Mucopolysaccharidosis IV
Chondroitinsulfatases
Mucopolysaccharidosis I
Mucopolysaccharidosis VI
Mucopolysaccharidosis VII
Mucopolysaccharidosis III
Mucopolysaccharidosis II
Mucopolysaccharidoses
Iduronidase
N-Acetylgalactosamine-4-Sulfatase
Chondro-4-Sulfatase
Iduronate Sulfatase
Enzyme Replacement Therapy
Glucuronidase
Glycosaminoglycans
Sulfatases
Lysosomes
Acetylglucosaminidase
Stomatognathic System
Lysosomal Storage Diseases
Molecular basis of GM1 gangliosidosis and Morquio disease, type B. Structure-function studies of lysosomal beta-galactosidase and the non-lysosomal beta-galactosidase-like protein. (1/75)
GM1 gangliosidosis and Morquio B disease are distinct disorders both clinically and biochemically yet they arise from the same beta-galactosidase enzyme deficiency. On the other hand, galactosialidosis and sialidosis share common clinical and biochemical features, yet they arise from two separate enzyme deficiencies, namely, protective protein/cathepsin A and neuraminidase, respectively. However distinct, in practice these disorders overlap both clinically and biochemically so that easy discrimination between them is sometimes difficult. The principle reason for this may be found in the fact that these three enzymes form a unique complex in lysosomes that is required for their stability and posttranslational processing. In this review, I focus mainly on the primary and secondary beta-galactosidase deficiency states and offer some hypotheses to account for differences between GM1 gangliosidosis and Morquio B disease. (+info)The mouse N-acetylgalactosamine-6-sulfate sulfatase (Galns) gene: cDNA isolation, genomic characterization, chromosomal assignment and analysis of the 5'-flanking region. (2/75)
Deficiency of lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS) leads to mucopolysaccharidosis IV A (MPS IV A), for which there is no definitive treatment so far. Although a number of mutations of the GALNS gene of MPS IV A patients have been described, pathogenesis of the disorder still remains elusive. In order to facilitate in vivo studies using model animals for MPS IV A, we isolated and performed molecular characterization of the mouse homolog of human GALNS. The 2.3-kb cDNA contains a 1560-bp open reading frame encoding 520 amino acid residues. The coding region has 84% similarity to the human GALNS cDNA at amino acid level. The mouse Galns gene was mapped by interspecific backcross analysis to the distal region of chromosome 8 where it co-segregates with Aprt. Northern blot analysis showed a wide expression of a single-copy gene, being higher especially in liver and kidney. The Galns gene was isolated from S129vJ genomic library and its genomic organization was characterized. The mouse Galns gene was about 50-kb long and organized into 14 exons and 13 introns. All intron-exon splice junctions conformed to the GT/AG consensus sequence except exon 8/intron 8 junction. Primer extension shows multiple transcription initiation sites between -44 and -75 although major transcription initiation site was observed at -90 bp from the ATG codon. The 5'-flanking region lacks canonical TATA and CAAT box sequences, but is G+C rich with 10 GC boxes (potential Sp1 binding sites), characteristic of a housekeeping gene promoter. (+info)Biochemical and structural analysis of missense mutations in N-acetylgalactosamine-6-sulfate sulfatase causing mucopolysaccharidosis IVA phenotypes. (3/75)
Mucopolysaccharidosis IVA (MPS IVA; OMIM#253000), a lysosomal storage disorder caused by a deficiency of N -acetylgalactosamine-6-sulfate sulfatase (GALNS), has variable clinical phenotypes. To date we have identified 65 missense mutations in the GALNS gene from MPS IVA patients, but the correlation between genotype and phenotype has remained unclear. We studied 17 missense mutations using biochemical approaches and 32 missense mutations, using structural analyses. Fifteen missense mutations and two newly engineered active site mutations (C79S, C79T) were characterized by transient expression analysis. Mutant proteins, except for C79S and C79T, were destabilized and detected as insoluble precursor forms while the C79S and C79T mutants were of a soluble mature size. Mutants found in the severe phenotype had no activity. Mutants found in the mild phenotype had a considerable residual activity (1.3-13.3% of wild-type GALNS activity). Sulfatases, including GALNS, are members of a highly conserved gene family sharing an extensive sequence homology. Thus, a tertiary structural model of human GALNS was constructed from the X-ray crystal structure of N -acetylgalacto-samine-4-sulfatase and arylsulfatase A, using homology modeling, and 32 missense mutations were investigated. Consequently, we propose that there are at least three different reasons for the severe phenotype: (i) destruction of the hydrophobic core or modification of the packing; (ii) removal of a salt bridge to destabilize the entire conformation; (iii) modification of the active site. In contrast, mild mutations were mostly located on the surface of the GALNS protein. These studies shed further light on the genotype-phenotype correlation of MPS IVA and structure-function relationship in the sulfatase family. (+info)Impaired elastic-fiber assembly by fibroblasts from patients with either Morquio B disease or infantile GM1-gangliosidosis is linked to deficiency in the 67-kD spliced variant of beta-galactosidase. (4/75)
We have previously shown that intracellular trafficking and extracellular assembly of tropoelastin into elastic fibers is facilitated by the 67-kD elastin-binding protein identical to an enzymatically inactive, alternatively spliced variant of beta-galactosidase (S-Gal). In the present study, we investigated elastic-fiber assembly in cultures of dermal fibroblasts from patients with either Morquio B disease or GM1-gangliosidosis who bore different mutations of the beta-galactosidase gene. We found that fibroblasts taken from patients with an adult form of GM1-gangliosidosis and from patients with an infantile form, carrying a missense mutations in the beta-galactosidase gene-mutations that caused deficiency in lysosomal beta-galactosidase but not in S-Gal-assembled normal elastic fibers. In contrast, fibroblasts from two cases of infantile GM1-gangliosidosis that bear nonsense mutations of the beta-galactosidase gene, as well as fibroblasts from four patients with Morquio B who had mutations causing deficiency in both forms of beta-galactosidase, did not assemble elastic fibers. We also demonstrated that S-Gal-deficient fibroblasts from patients with either GM1-gangliosidosis or Morquio B can acquire the S-Gal protein, produced by coculturing of Chinese hamster ovary cells permanently transected with S-Gal cDNA, resulting in improved deposition of elastic fibers. The present study provides a novel and natural model validating functional roles of S-Gal in elastogenesis and elucidates an association between impaired elastogenesis and the development of connective-tissue disorders in patients with Morquio B disease and in patients with an infantile form of GM1-gangliosidosis. (+info)Saposins (sap) A and C activate the degradation of galactosylsphingosine. (5/75)
As previously shown for [(3)H-galactosyl]ceramide, the breakdown of [(3)H-galactosyl]sphingosine was reduced in prosaposin-deficient skin fibroblast homogenates. Galactosylsphingosine hydrolysis was also deficient in cell homogenates from Krabbe's disease (beta-galactocerebrosidase-deficient) patients, but not acid beta-galactosidase-deficient patients. Moreover, hydrolysis of galactosylsphingosine in the prosaposin-deficient cell homogenates could be partially restored by adding pure saposin A or C, thereby identifying these saposins as essential facilitators of galactosylsphingosine hydrolysis. By contrast, saposins B and D had little effect on galactosylsphingosine hydrolysis in the prosaposin-deficient cells. The reduced galactosylsphingosine turnover in prosaposin-deficiency suggests that there could be a pathogenetic cerebral accumulation of galactosylsphingosine in this disorder. (+info)Novel mutations (Asn 484 Lys, Thr 500 Ala, Gly 438 Glu) in Morquio B disease. (6/75)
Primary deficiency of beta-galactosidase results in GM1 gangliosidosis and Morquio B disease. Of the more than 40 disease-causing mutations described in the Gal gene to date, about 75% are of the missense type and are scattered along the length of the gene. No single, major common mutation has been associated with GM1 gangliosidosis. However, a Trp 273 Leu mutation has been commonly found in the majority of patients with Morquio B disease defined genotypically to date. We now report three new mutations in three Morquio B patients where the Trp 273 Leu mutation is absent. Two of the mutations, C1502G (Asn 484 Lys) and A1548G (Thr 500 Ala), were found in twins (one male, one female) who display a mild form of Morquio B disease and keratan sulfate in the urine. In their fibroblasts, residual activity was 1.9% and 2.1% of controls. On Western blots, the 84-kDa precursor and the 64-kDa mature protein were barely detectable. The occurrence of a 45-kDa degradation product indicates that the mutated protein reached the lysosome but was abnormally processed. In the third case, we identified only a G1363A (Gly 438 Glu) mutation (a major deletion on the second allele has not been ruled out). This female patient too displays a very mild form of the disease with a residual activity of 5.7% of control values. In fibroblasts from this case, the 84-kDa precursor and the 45-kDa degradation product were present, while the mature 64-kDa form was barely detectable. The occurrence of these three mutations in the same area of the protein may define a domain involved in keratan sulfate degradation. (+info)Upper airways abnormalities and tracheal problems in Morquio's disease. (7/75)
Morquio's disease is a metabolic disorder that can cause various respiratory abnormalities. Patients who live into adulthood are likely to develop upper airway problems and respiratory failure. With advances in home ventilation, these patients are increasingly likely to be referred to specialist respiratory units. We describe our experiences with two such patients. (+info)Mouse model of N-acetylgalactosamine-6-sulfate sulfatase deficiency (Galns-/-) produced by targeted disruption of the gene defective in Morquio A disease. (8/75)
Mucopolysaccharidosis IVA is an autosomal recessive disorder caused by a deficiency of N-acetylgalactosamine-6-sulfate sulfatase (GALNS), a lysosomal enzyme required for the stepwise degradation of keratan sulfate (KS) and chondroitin-6-sulfate (C6S). To generate a model for studies of the pathophysiology and of potential therapies, we disrupted exon 2 of Galns, the homologous murine gene. Homozygous Galns-/- mice have no detectable GALNS enzyme activity and show increased urinary glycosaminoglycan (GAGs) levels. These mice accumulate GAGs in multiple tissues including liver, kidney, spleen, heart, brain and bone marrow. At 2 months old, lysosomal storage is present primarily within reticuloendothelial cells such as Kupffer cells and cells of the sinusoidal lining of the spleen. Additionally, by 12 months old, vacuolar change is observed in the visceral epithelial cells of glomeruli and cells at the base of heart valves but it is not present in parenchymal cells such as hepatocytes and renal tubular epithelial cells. In the brain, hippocampal and neocortical neurons and meningeal cells had lysosomal storage. KS and C6S were more abundant in the cytoplasm of corneal epithelial cells of Galns-/- mice compared with wild-type mice by immunohistochemistry. Radiographs revealed no change in the skeletal bones of mice up to 12 months old. Thus, targeted disruption of the murine Galns gene has produced a murine model, which shows visceral storage of GAGs but lacks the skeletal features. The complete absence of GALNS in mutant mice makes them useful for studies of pharmacokinetics and tissue targeting of recombinant GALNS designed for enzyme replacement. (+info)Mucopolysaccharidosis IV (MPS IV), also known as Morquio Syndrome, is a rare genetic disorder that belongs to the family of diseases called mucopolysaccharidoses. It is characterized by the accumulation of glycosaminoglycans (GAGs or mucopolysaccharides) in various tissues and organs due to deficiencies in specific enzymes needed to break down these complex carbohydrates.
There are two types of MPS IV: Type A and Type B, which are caused by deficiencies in different enzymes (GALNS and B3GALNT1, respectively). Both types result in similar symptoms but may vary in severity. The accumulation of GAGs primarily affects the bones, cartilage, eyes, ears, heart, and respiratory system.
Common features of MPS IV include:
* Dwarfism with short trunk and long limbs
* Progressive skeletal abnormalities such as kyphosis (hunchback), scoliosis (curvature of the spine), pectus carinatum (protruding breastbone), and joint laxity or stiffness
* Coarse facial features
* Corneal clouding
* Hearing loss
* Heart valve abnormalities
* Respiratory issues
* Hypermobile and dislocated joints
* Carpal tunnel syndrome
* Spinal cord compression
Treatment for MPS IV primarily focuses on managing symptoms, improving quality of life, and preventing complications. Enzyme replacement therapy (ERT) is available for Type B but not for Type A. Other treatments may include physical therapy, surgery, and medications to address specific symptoms.
Chondroitin sulfatases are a group of enzymes that break down chondroitin sulfate, which is a type of glycosaminoglycan (GAG) found in connective tissues such as cartilage, bone, and skin. Glycosaminoglycans are long, complex chains of sugars that help provide structure, hydration, and elasticity to these tissues.
Chondroitin sulfate is composed of alternating units of glucuronic acid and N-acetylgalactosamine, with various sulfate groups attached at different positions along the chain. Chondroitin sulfatases cleave specific bonds within this structure to help regulate the turnover and remodeling of GAGs in tissues.
There are several types of chondroitin sulfatases (designated as chondroitin sulfatase A, B, C, D, etc.), each with distinct substrate specificities and cellular localizations. Defects in these enzymes can lead to various genetic disorders, such as skeletal dysplasias and neurodegenerative diseases, due to the accumulation of unprocessed or partially degraded chondroitin sulfate in tissues.
Mucopolysaccharidosis I (MPS I) is a rare genetic disorder caused by the deficiency of an enzyme called alpha-L-iduronidase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs), also known as mucopolysaccharides, in the body.
When the enzyme is deficient, GAGs accumulate in various tissues and organs, leading to a range of symptoms that can affect different parts of the body, including the skeletal system, heart, respiratory system, eyes, and central nervous system. There are three subtypes of MPS I: Hurler syndrome (the most severe form), Hurler-Scheie syndrome (an intermediate form), and Scheie syndrome (the least severe form).
The symptoms and severity of MPS I can vary widely depending on the specific subtype, with Hurler syndrome typically causing more significant health problems and a shorter life expectancy than the other two forms. Treatment options for MPS I include enzyme replacement therapy, bone marrow transplantation, and various supportive therapies to manage symptoms and improve quality of life.
Mucopolysaccharidosis VI (MPS VI), also known as Maroteaux-Lamy syndrome, is a rare genetic disorder caused by the deficiency of an enzyme called N-acetylgalactosamine 4-sulfatase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs) or mucopolysaccharides, which are found in various tissues and organs throughout the body.
When the enzyme is deficient, GAGs accumulate within the lysosomes of cells, leading to cellular dysfunction and tissue damage. This accumulation results in a range of symptoms that can affect multiple organ systems, including the skeletal system, cardiovascular system, respiratory system, and central nervous system.
The signs and symptoms of MPS VI can vary widely among affected individuals, but common features include: coarse facial features, short stature, stiff joints, restricted mobility, recurrent respiratory infections, hearing loss, heart valve abnormalities, and clouding of the cornea. The severity of the disease can range from mild to severe, and life expectancy is generally reduced in individuals with more severe forms of the disorder.
MPS VI is inherited as an autosomal recessive trait, which means that an individual must inherit two copies of the mutated gene (one from each parent) to develop the condition.
Mucopolysaccharidosis (MPS) VII, also known as Sly syndrome, is a rare genetic disorder caused by the deficiency of the enzyme beta-glucuronidase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs), or mucopolysaccharides, in the body. When this enzyme is not present in sufficient amounts, GAGs accumulate in various tissues and organs, leading to progressive damage.
The symptoms of MPS VII can vary widely, but often include coarse facial features, short stature, skeletal abnormalities, hearing loss, heart problems, and intellectual disability. Some individuals with MPS VII may also have cloudy corneas, enlarged liver and spleen, and difficulty breathing due to airway obstruction. The severity of the condition can range from mild to severe, and life expectancy is often reduced in those with more severe symptoms.
MPS VII is inherited in an autosomal recessive manner, which means that an individual must inherit two copies of the mutated gene (one from each parent) in order to develop the condition. Treatment for MPS VII typically involves enzyme replacement therapy, which can help to slow down the progression of the disease and improve some symptoms. However, there is currently no cure for this condition.
Mucopolysaccharidosis III, also known as Sanfilippo syndrome, is a genetic disorder caused by the deficiency of specific enzymes needed to break down complex sugar molecules called glycosaminoglycans (GAGs) or mucopolysaccharides. This results in an accumulation of these substances in various tissues and organs, leading to progressive damage.
There are four main types of Mucopolysaccharidosis III (A, B, C, and D), each caused by a deficiency in one of the following enzymes: heparan N-sulfatase (type A), alpha-N-acetylglucosaminidase (type B), acetyl-CoAlpha-glucosaminide acetyltransferase (type C), or N-acetylglucosamine 6-sulfatase (type D).
The symptoms of Mucopolysaccharidosis III typically become apparent between the ages of 2 and 6, and may include developmental delays, hyperactivity, behavioral problems, sleep disturbances, coarse facial features, hirsutism, hepatosplenomegaly (enlarged liver and spleen), and joint stiffness. Over time, individuals with Mucopolysaccharidosis III may experience a decline in cognitive abilities, loss of previously acquired skills, and mobility issues.
Currently, there is no cure for Mucopolysaccharidosis III, and treatment is focused on managing the symptoms and improving quality of life. Enzyme replacement therapy, gene therapy, and stem cell transplantation are some of the experimental treatments being investigated for this condition.
Mucopolysaccharidosis II (MPS II), also known as Hunter syndrome, is a rare X-linked recessive genetic disorder caused by the deficiency of an enzyme called iduronate sulfatase. This enzyme is responsible for breaking down complex sugars called glycosaminoglycans (GAGs) or mucopolysaccharides in the body.
When this enzyme is missing or not functioning properly, GAGs accumulate in various tissues and organs, leading to progressive cellular damage and organ dysfunction. The symptoms of MPS II can vary widely but often include developmental delays, coarse facial features, hearing loss, airway obstruction, heart problems, enlarged liver and spleen, and joint stiffness.
The severity of the disease can range from mild to severe, with some individuals experiencing only moderate symptoms while others may have significant intellectual disability and life-threatening complications. Treatment options for MPS II include enzyme replacement therapy (ERT) and hematopoietic stem cell transplantation (HSCT), but there is currently no cure for the disease.
Mucopolysaccharidoses (MPS) are a group of inherited metabolic disorders caused by the deficiency of specific enzymes needed to break down complex sugars called glycosaminoglycans (GAGs or mucopolysaccharides). As a result, these GAGs accumulate in various tissues and organs, leading to progressive cellular damage and multi-organ dysfunction. There are several types of MPS, including Hurler syndrome, Hunter syndrome, Sanfilippo syndrome, Morquio syndrome, Maroteaux-Lamy syndrome, and Sly syndrome, each resulting from a deficiency in one of the eleven different enzymes involved in GAGs metabolism. The clinical presentation, severity, and prognosis vary among the types but commonly include features such as developmental delay, coarse facial features, skeletal abnormalities, hearing loss, heart problems, and reduced life expectancy.
Iduronidase is a type of enzyme that helps break down complex sugars called glycosaminoglycans (GAGs) in the body. Specifically, iduronidase is responsible for breaking down a type of GAG called dermatan sulfate and heparan sulfate.
Deficiency or absence of this enzyme can lead to a genetic disorder known as Mucopolysaccharidosis Type I (MPS I), which is characterized by the accumulation of GAGs in various tissues and organs, leading to progressive damage and impairment. There are two forms of MPS I: Hurler syndrome, which is the severe form, and Scheie syndrome, which is the milder form.
Iduronidase replacement therapy is available for the treatment of MPS I, in which the missing enzyme is delivered directly to the patient's body through intravenous infusion. This helps break down the accumulated GAGs and prevent further damage to the tissues and organs.
N-Acetylgalactosamine-4-Sulfatase is an enzyme that is responsible for breaking down complex carbohydrates in the body. Its specific function is to remove a sulfate group from a particular type of sugar molecule called N-acetylgalactosamine-4-sulfate, which is found on certain proteoglycans (large, complex sugars attached to proteins) in the body.
This enzyme plays an important role in the normal functioning of cells and tissues, particularly in the development and maintenance of bones, cartilage, and other connective tissues. Deficiencies in this enzyme can lead to a rare genetic disorder called Morquio A syndrome (also known as MPS IVA), which is characterized by skeletal abnormalities, short stature, and other health problems.
Chondro-4-sulfatase is an enzyme that belongs to the family of hydrolases, specifically those acting on ester bonds in sulfuric acid esters. It is responsible for catalyzing the hydrolysis of the 4-sulfate ester group from N-acetylgalactosamine 4-sulfate residues found in chondroitin 4-sulfate, a type of glycosaminoglycan (GAG) that is abundant in connective tissues such as cartilage.
Chondroitin 4-sulfate plays important roles in the structure and function of the extracellular matrix, including regulating cell adhesion, migration, and differentiation. The action of chondro-4-sulfatase helps to control the balance between sulfated and non-sulfated GAG chains, which is critical for maintaining normal tissue homeostasis.
Defects in chondro-4-sulfatase activity can lead to a rare genetic disorder called chondrodysplasia punctata type 1B (CDPX1B), also known as multiple sulfatase deficiency (MSD). This condition is characterized by skeletal abnormalities, developmental delay, and other neurological symptoms.
Iduronate sulfatase is an enzyme that plays a crucial role in the breakdown and recycling of complex sugars called glycosaminoglycans (GAGs). These GAGs are important components of various tissues, including connective tissues, bones, and cartilage.
Iduronate sulfatase is specifically responsible for breaking down a type of GAG known as dermatan sulfate and heparan sulfate by removing sulfate groups from specific sugar molecules in these GAGs. This enzyme is located in the lysosomes, which are membrane-bound organelles within cells that break down and recycle various materials.
Deficiency of iduronate sulfatase leads to a genetic disorder called Mucopolysaccharidosis Type II (MPS II), also known as Hunter syndrome. In this condition, the lack of functional iduronate sulfatase enzyme results in an accumulation of dermatan sulfate and heparan sulfate in various tissues and organs, leading to progressive damage and a range of symptoms, including developmental delays, coarse facial features, hearing loss, heart problems, and joint stiffness.
Enzyme Replacement Therapy (ERT) is a medical treatment approach in which functional copies of a missing or deficient enzyme are introduced into the body to compensate for the lack of enzymatic activity caused by a genetic disorder. This therapy is primarily used to manage lysosomal storage diseases, such as Gaucher disease, Fabry disease, Pompe disease, and Mucopolysaccharidoses (MPS), among others.
In ERT, the required enzyme is produced recombinantly in a laboratory using biotechnological methods. The purified enzyme is then administered to the patient intravenously at regular intervals. Once inside the body, the exogenous enzyme is taken up by cells, particularly those affected by the disorder, and helps restore normal cellular functions by participating in essential metabolic pathways.
ERT aims to alleviate disease symptoms, slow down disease progression, improve quality of life, and increase survival rates for patients with lysosomal storage disorders. However, it does not cure the underlying genetic defect responsible for the enzyme deficiency.
Glucuronidase is an enzyme that catalyzes the hydrolysis of glucuronic acid from various substrates, including molecules that have been conjugated with glucuronic acid as part of the detoxification process in the body. This enzyme plays a role in the breakdown and elimination of certain drugs, toxins, and endogenous compounds, such as bilirubin. It is found in various tissues and organisms, including humans, bacteria, and insects. In clinical contexts, glucuronidase activity may be measured to assess liver function or to identify the presence of certain bacterial infections.
Glycosaminoglycans (GAGs) are long, unbranched polysaccharides composed of repeating disaccharide units. They are a major component of the extracellular matrix and connective tissues in the body. GAGs are negatively charged due to the presence of sulfate and carboxyl groups, which allows them to attract positively charged ions and water molecules, contributing to their ability to retain moisture and maintain tissue hydration and elasticity.
GAGs can be categorized into four main groups: heparin/heparan sulfate, chondroitin sulfate/dermatan sulfate, keratan sulfate, and hyaluronic acid. These different types of GAGs have varying structures and functions in the body, including roles in cell signaling, inflammation, and protection against enzymatic degradation.
Heparin is a highly sulfated form of heparan sulfate that is found in mast cells and has anticoagulant properties. Chondroitin sulfate and dermatan sulfate are commonly found in cartilage and contribute to its resiliency and ability to withstand compressive forces. Keratan sulfate is found in corneas, cartilage, and bone, where it plays a role in maintaining the structure and function of these tissues. Hyaluronic acid is a large, nonsulfated GAG that is widely distributed throughout the body, including in synovial fluid, where it provides lubrication and shock absorption for joints.
Sulfatases are a group of enzymes that play a crucial role in the metabolism of sulfated steroids, glycosaminoglycans (GAGs), and other sulfated molecules. These enzymes catalyze the hydrolysis of sulfate groups from these substrates, converting them into their respective unsulfated forms.
The human genome encodes for several different sulfatases, each with specificity towards particular types of sulfated substrates. For instance, some sulfatases are responsible for removing sulfate groups from steroid hormones and neurotransmitters, while others target GAGs like heparan sulfate, dermatan sulfate, and keratan sulfate.
Defects in sulfatase enzymes can lead to various genetic disorders, such as multiple sulfatase deficiency (MSD), X-linked ichthyosis, and mucopolysaccharidosis (MPS) type IIIC (Sanfilippo syndrome type C). These conditions are characterized by the accumulation of sulfated molecules in different tissues, resulting in progressive damage to multiple organs and systems.
Lysosomes are membrane-bound organelles found in the cytoplasm of eukaryotic cells. They are responsible for breaking down and recycling various materials, such as waste products, foreign substances, and damaged cellular components, through a process called autophagy or phagocytosis. Lysosomes contain hydrolytic enzymes that can break down biomolecules like proteins, nucleic acids, lipids, and carbohydrates into their basic building blocks, which can then be reused by the cell. They play a crucial role in maintaining cellular homeostasis and are often referred to as the "garbage disposal system" of the cell.
Acetylglucosaminidase (ACG) is an enzyme that catalyzes the hydrolysis of N-acetyl-beta-D-glucosaminides, which are found in glycoproteins and glycolipids. This enzyme plays a crucial role in the degradation and recycling of these complex carbohydrates within the body.
Deficiency or malfunction of Acetylglucosaminidase can lead to various genetic disorders, such as mucolipidosis II (I-cell disease) and mucolipidosis III (pseudo-Hurler polydystrophy), which are characterized by the accumulation of glycoproteins and glycolipids in lysosomes, resulting in cellular dysfunction and progressive damage to multiple organs.
The stomatognathic system is a term used in medicine and dentistry to refer to the coordinated functions of the mouth, jaw, and related structures. It includes the teeth, gums, tongue, palate, lips, cheeks, salivary glands, as well as the muscles of mastication (chewing), swallowing, and speech. The stomatognathic system also involves the temporomandibular joint (TMJ) and associated structures that allow for movement of the jaw. This complex system works together to enable functions such as eating, speaking, and breathing. Dysfunction in the stomatognathic system can lead to various oral health issues, including temporomandibular disorders, occlusal problems, and orofacial pain.
Lysosomal storage diseases (LSDs) are a group of rare inherited metabolic disorders caused by defects in lysosomal function. Lysosomes are membrane-bound organelles within cells that contain enzymes responsible for breaking down and recycling various biomolecules, such as proteins, lipids, and carbohydrates. In LSDs, the absence or deficiency of specific lysosomal enzymes leads to the accumulation of undigested substrates within the lysosomes, resulting in cellular dysfunction and organ damage.
These disorders can affect various organs and systems in the body, including the brain, nervous system, bones, skin, and visceral organs. Symptoms may include developmental delays, neurological impairment, motor dysfunction, bone abnormalities, coarse facial features, hepatosplenomegaly (enlarged liver and spleen), and recurrent infections.
Examples of LSDs include Gaucher disease, Tay-Sachs disease, Niemann-Pick disease, Fabry disease, Pompe disease, and mucopolysaccharidoses (MPS). Treatment options for LSDs may include enzyme replacement therapy, substrate reduction therapy, or bone marrow transplantation. Early diagnosis and intervention can help improve the prognosis and quality of life for affected individuals.
Enzyme therapy refers to the use of enzymes as a medical treatment. Enzymes are proteins that help speed up chemical reactions in the body. In enzyme therapy, specific enzymes are administered to help support and optimize various biological processes.
There are several types of enzyme therapies, including:
1. Systemic enzyme therapy: This involves taking enzymes orally, so they can be absorbed into the bloodstream and exert their effects throughout the body. Systemic enzymes may help reduce inflammation, support immune function, and improve circulation.
2. Digestive enzyme therapy: This type of enzyme therapy involves taking enzymes to aid in digestion. Digestive enzymes help break down food into smaller molecules, making it easier for the body to absorb nutrients.
3. Topical enzyme therapy: Enzymes can also be applied directly to the skin to help promote healing and reduce inflammation. This type of enzyme therapy is often used in the treatment of wounds, burns, and other skin conditions.
It's important to note that while some studies suggest that enzyme therapy may be beneficial for certain health conditions, more research is needed to fully understand its potential benefits and risks. As with any medical treatment, it's important to consult with a healthcare provider before starting enzyme therapy.
Genetic therapy, also known as gene therapy, is a medical intervention that involves the use of genetic material, such as DNA or RNA, to treat or prevent diseases. It works by introducing functional genes into cells to replace missing or faulty ones caused by genetic disorders or mutations. The introduced gene is incorporated into the recipient's genome, allowing for the production of a therapeutic protein that can help manage the disease symptoms or even cure the condition.
There are several approaches to genetic therapy, including:
1. Replacing a faulty gene with a healthy one
2. Inactivating or "silencing" a dysfunctional gene causing a disease
3. Introducing a new gene into the body to help fight off a disease, such as cancer
Genetic therapy holds great promise for treating various genetic disorders, including cystic fibrosis, muscular dystrophy, hemophilia, and certain types of cancer. However, it is still an evolving field with many challenges, such as efficient gene delivery, potential immune responses, and ensuring the safety and long-term effectiveness of the therapy.
Luis Morquio
N-acetylglucosamine-6-sulfatase
Galactosamine-6 sulfatase
Scheie syndrome
Hunter syndrome
List of OMIM disorder codes
Osteochondrodysplasia
List of skin conditions
List of diseases (M)
Morquio syndrome
GM1 gangliosidoses
N-sulfoglucosamine sulfohydrolase
List of MeSH codes (C18)
List of MeSH codes (C17)
Iduronate-2-sulfatase
Β-Glucuronidase
HGSNAT
Sanfilippo syndrome
Arylsulfatase B
Vestronidase alfa
Chromosome 4
NAGLU
SGSH
Dermatan sulfate
Mucolipidosis
List of MeSH codes (C16)
Emil Kakkis
Hurler syndrome
Maroteaux-Lamy syndrome
Maria Luisa Escolar
Mucopolysaccharidosis type IV: MedlinePlus Medical Encyclopedia
Morquio Syndrome (Mucopolysaccharidosis Type IV): Background, Pathophysiology, Epidemiology
Morquio Syndrome (Mucopolysaccharidosis Type IV): Background, Pathophysiology, Epidemiology
Mucopolysaccharidosis Type IV - Healthviber
Genetics of Mucopolysaccharidosis Type IV Differential Diagnoses
Genetics of Mucopolysaccharidosis Type IV: Background, Pathophysiology, Epidemiology
Tracheomalacia in an adult with respiratory failure and Morquio syndrome
Mucopolysaccharidoses Types I-VII Differential Diagnoses
Luis Morquio - Wikipedia
Galns (galactosamine (N-acetyl)-6-sulfatase) - Rat Genome Database
Clathrin and phosphatidylinositol-4,5-bisphosphate regulate autophagic lysosome reformation | Nature Cell Biology
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Mucopolysaccharidosis: Decoding the 10 Warning Signs
Bio2Vec
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Ocular Features of Mucopolysaccharidosis - EyeWiki
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Coxa valga (Concept Id: C0239137) - MedGen - NCBI
Aortic valve stenosis (Concept Id: C0003507) - MedGen - NCBI
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Markers of cognitive function in patients with metabolic disease: Morquio Syndrome and Tyrosinemia Type III<...
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Lysosomal storage d4
- Mucopolysaccharidoses (MPSs) are a heterogenous and rare group of lysosomal storage disorders. (eyewiki.org)
- GLB1-related disorders comprise two phenotypically distinct lysosomal storage disorders: GM1 gangliosidosis and mucopolysaccharidosis type IVB (MPS IVB). (nih.gov)
- The mucopolysaccharidoses (MPS) are a varied group of rare inherited lysosomal storage disorders, in which an affected person lacks a specific enzyme that is needed to break down glycosaminoglycans (GAGs). (biomedcentral.com)
- Arizona will increase the laboratory capacity to screen for two lysosomal storage disorders, Pompe Disease and Mucopolysaccharidosis Type-1 (MPS-1). (cdc.gov)
Morquio Syndrome11
- MPS IV is also known as Morquio syndrome. (medlineplus.gov)
- Morquio syndrome (mucopolysaccharidosis type IV [MPS IV]) is a rare lysosomal storage disease (LSD) that is inherited in an autosomal-recessive fashion. (medscape.com)
- [ 5 ] In 1965, McKusick et al classified Hurler and Hunter syndromes, as well as Morquio syndrome, as hereditary acid mucopolysaccharidoses (MPS I to MPS V). MPS V was referred to as Scheie Syndrome. (medscape.com)
- Mucopolysaccharidosis type IV (MPS IV), also known as Morquio syndrome, is a progressive condition that mainly affects the skeleton. (healthviber.com)
- Morquio syndrome (mucopolysaccharidosis type IV) is a member of a group of inherited metabolic disorders collectively termed mucopolysaccharidoses (MPSs). (medscape.com)
- Patients with Morquio syndrome (mucopolysaccharidosis type IV) can usually be clinically distinguished from patients with other MPSs because they do not have coarse facial features or mental retardation and they have additional skeletal manifestations derived from a unique spondyloepiphyseal dysplasia and ligamentous laxity. (medscape.com)
- Compared with other patients who have MPS, those with Morquio syndrome (mucopolysaccharidosis type IV) tend to have greater spine involvement with scoliosis, kyphosis, and severe gibbus, as well as platyspondyly, rib flaring, pectus carinatum, and ligamentous laxity. (medscape.com)
- Odontoid hypoplasia is the most critical skeletal feature to recognize in any patient with Morquio syndrome (mucopolysaccharidosis type IV). (medscape.com)
- A medical condition, Morquio syndrome (mucopolysaccharidosis IV), is named in his honor. (wikipedia.org)
- A medical condition known as mucopolysaccharidosis type IV, which he described, was named Morquio syndrome in his honor. (wikipedia.org)
- In 2006, Annabelle was diagnosed with Mucopolysaccharidoses IVA (aka MPSIVA or Morquio Syndrome). (mpssociety.org)
MPSs1
- The condition belongs to a group of diseases called mucopolysaccharidoses (MPSs). (medlineplus.gov)
Deficiency3
- Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder resulting from deficiency of the enzyme α-L-iduronidase. (medicalhomeportal.org)
- Sanfilippo syndrome results from the deficiency or absence of 4 different enzymes that are necessary to degrade the GAG heparan sulfate. (symptoma.com)
- Orphan drug carglumic acid ( Carbaglu , Recordati), for treating the rare genetic disorder N -acetylglutamate synthase deficiency, which causes hyperammonemia , holds the number 4 spot on the list of most expensive drugs. (medscape.com)
Enzyme replace1
- Oxidative stress and inflammation in mucopolysaccharidosis type IVA patients treated with enzyme replacement therapy. (medscape.com)
Scheie1
- The mild form of mucopolysaccharidosis type I (Scheie syndrome) is associated with increased ascending aortic stiffness. (medscape.com)
Pompe Disease2
- Build newborn screening laboratory capacity to screen for new Recommended Uniform Screening Panel (RUSP) conditions: Pompe Disease, Mucopolysaccharidosis Type 1 (MPS-1), X-linked Adrenoleukodystrophy (X-ALD), and Spinal Muscular Atrophy (SMA). (cdc.gov)
- These activities will enable the state to move ahead with implementing Pompe Disease and Mucopolysaccharidosis Type I (MPSI) in Texas. (cdc.gov)
Syndrome9
- A Double-Blind Study to Evaluate the Efficacy and Safety of BMN 110 in Patients With Mucopolysaccharidosis IVA (Morquio A Syndrome). (medscape.com)
- Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome). (medscape.com)
- Natural history of extensive Mongolian spots in mucopolysaccharidosis type II (Hunter syndrome): a survey among 52 Japanese patients. (medscape.com)
- High prevalence of carpal tunnel syndrome in children with mucopolysaccharidosis type II (Hunter syndrome). (medscape.com)
- Mucopolysaccharidosis type III (MPS III), also known as Sanfilippo syndrome, is a disorder that primarily affects the brain and spinal cord (central nervous system). (medlineplus.gov)
- Mucopolysaccharidosis VI (MPS VI) or Maroteaux-Lamy syndrome is a rare metabolic disorder, resulting from the deficient activity of the lysosomal enzyme arylsulfatase B (ARSB). (ac.ir)
- The present report describes the clinical, echocardiographic, and pathological findings in four patients with Maroteaux-Lamy syndrome. (elsevierpure.com)
- Mucopolysaccharidosis III (Sanfilippo Syndrome)- disease presentation and experimental therapies. (symptoma.com)
- Although dentigerous cysts are highly prevalent, bilateral occurrence is rare and usually associated with syndromes or systemic diseases 1 , such as Maroteaux-Lamy syndrome 2 , cleidocranial dysplasia, and mucopolysaccharidosis 1 . (bvsalud.org)
Incidence6
- Cumulative incidence rates of the mucopolysaccharidoses in Germany. (medscape.com)
- Incidence and prevalence of mucopolysaccharidosis type 1 in the Irish republic. (medscape.com)
- Malm G, Lund AM, Mansson JE, Heiberg A. Mucopolysaccharidoses in the Scandinavian countries: incidence and prevalence. (medscape.com)
- Incidence and natural history of mucopolysaccharidosis type III in France and comparison with United Kingdom and Greece. (medscape.com)
- the estimated incidence of all four types combined is 1 in 70,000 newborns. (medlineplus.gov)
- In this paper we present four cases with transient NIHF and a literature review on the incidence of LSD in NIHF. (biomedcentral.com)
Lysosome3
- Combining a screen of candidates identified through proteomic analysis of purified ALR tubules, and large-scale RNAi knockdown, we unveiled a tightly regulated molecular pathway that controls lysosome homeostasis, in which clathrin and PtdIns(4,5)P 2 are the central components. (nature.com)
- Our data not only uncover a molecular pathway by which lysosome homeostasis is maintained through the ALR process, but also reveal unexpected functions of clathrin and PtdIns(4,5)P 2 in lysosome homeostasis. (nature.com)
- Figure 4: Phosphatidylinositol-4-phosphate 5-kinase (PIP5K1A) is required for proto-lysosome budding during ALR. (nature.com)
Multisystem1
- Mucopolysaccharidosis type I (MPS I) is a progressive multisystem disorder with features ranging over a continuum of severity. (nih.gov)
Symptoms3
- Contact your provider if symptoms of MPS IV occur. (medlineplus.gov)
- The rate at which symptoms worsen varies among affected individuals.The first signs and symptoms of MPS IV usually become apparent during early childhood. (healthviber.com)
- Unlike some other types of mucopolysaccharidosis, MPS IV does not affect intelligence.The life expectancy of individuals with MPS IV depends on the severity of symptoms. (healthviber.com)
Diseases3
- Mucopolysaccharidoses (MPS) and related diseases are genetic lysosomal storage diseases (LSD) caused by the body's inability to produce specific enzymes. (mpssociety.org)
- Considering this need for patient-focused materials, we present a directed approach for mucopolysaccharidosis (MPS) VI and MPS IVA, a pair of rare, inherited diseases that affects multiple organs and parts of the body. (biomedcentral.com)
- UPDATED May 4, 2017 // The world's top 10 most expensive drugs are all orphan drugs for rare and ultrarare diseases, according to a new analysis. (medscape.com)
Disorders2
- The differential diagnosis includes other mucopolysaccharidosis (MPS) disorders (see Table 1) and chondrodysplasias. (medscape.com)
- Lysosomal disorders like mucopolysaccharidosis are triggered when a particular enzyme exists in too small amount or it is missing altogether. (mpstarsasag.hu)
Patients14
- In 1929, Luis Morquio first reported 4 Swedish patients with MPS IV (now classified as MPS IVA). (medscape.com)
- Nakarat T, Läßig AK, Lampe C, Keilmann A. Alterations in speech and voice in patients with mucopolysaccharidoses. (medscape.com)
- Here, we analyzed 4 Iranian and 2 Afghan patients, with dysmorphism indicating MPS VI from North-east Iran. (ac.ir)
- Evaluation of oral manifestations of patients with mucopolysaccharidosis IV and VI: clinical and imaging study. (ac.ir)
- Genetic analysis of mucopolysaccharidosis type VI in Taiwanese patients. (ac.ir)
- Analysis of N-acetylgalactosamine-4-sulfatase protein and kinetics in mucopolysaccharidosis type VI patients. (ac.ir)
- Novel mutations of the arylsulphatase B (ARSB) gene in Indian patients with mucopolysaccharidosis type VI. (ac.ir)
- Patients with mucopolysaccharidosis type VI (MPS VI) present with a wide range of disease severity and clinical manifestations, with significant functional impairment and shortened lifespan. (bvsalud.org)
- The present study is a resurvey of 34 Brazilian MPS VI patients with rapidly progressive disease (classical phenotype) who initiated ERT with galsulfase under five years of age and had been on ERT until data collection in 2019, with few exceptions (n = 4 patients who died before 2019). (bvsalud.org)
- In MPS IVA patients the mean height of both genders start to fall markedly below the − 2 SD value at 4 years of age [33]. (symptoma.com)
- Thirty-eight patients, 17 with adrenomyeloneuropathy, 3 with mucopolysaccharidosis I, 3 with mucopolysaccharidosis IV, 2 with mucopolysaccharidosis VI, 2 with mucolipidosis, and 11 with human T-cell lymphotropic virus type-1 (HTLV-1)-associated myelopathy participated in the study. (scielo.org)
- La base de données consacrée à l'administration des patients et à l'activité biostatistique a été interrogée pour l'ensemble des patients de moins de 15 ans qui avaient consulté à l'hôpital de campagne militaire marocain dans la Bande de Gaza entre novembre 2012 et février 2013 et les données obtenues ont été passées en revue. (who.int)
- Les patients pédiatriques souffrant de traumatismes potentiellement fatals constituent une partie de la responsabilité première des établissements de santé militaires en temps de guerre. (who.int)
- 9. Galsulfase ( Naglazyme , Biomarin Phamaceutical), approved in 2005 to improve walking and stair-climbing capacity of patients with mucopolysaccharidosis VI . (medscape.com)
Clinical5
- 7. Saito S, Ohno K, Sugawara K, Sakuraba H. Structural and clinical implications of amino acid substitutions in N-acetylgalactosamine-4-sulfatase: insight into mucopolysaccharidosis type VI. (ac.ir)
- Clinical, biochemical and molecular features of Iranian families with mucopolysaccharidosis: A case series. (ac.ir)
- Clinical outcomes following hematopoietic stem cell transplantation for the treatment of mucopolysaccharidosis VI. (ac.ir)
- Clinical variability among the mucopolysaccharidoses is broad. (medicalhomeportal.org)
- The ability to spatially map the diffusion of free water protons in vivo using 1 H MR imaging and the observation that the diffusion of free water protons is reduced in acutely infarcted brain tissue are responsible for the widespread use of these techniques in clinical imaging [ 3 , 4 , 5 , 6 , 7 , 8 ]. (ajronline.org)
Metabolism1
- Progressive myelopathies can be secondary to inborn errors of metabolism (IEM) such as mucopolysaccharidosis, mucolipidosis, and adrenomyeloneuropathy. (scielo.org)
Mutations1
- In direct DNA sequencing, we detected four different homozygous mutations in different exons, three of which seem not to have been reported previously: p.H178N, p.H242R, and p.*534W. (ac.ir)
Abnormal1
- Mucopolysaccharidoses (MPS) are defined by abnormal buildup of glycosaminoglycans, large sugar-protein molecules that are important for skeletal and joint function. (embarkvet.com)
Abstract1
- Abstract Mucopolysaccharidosis type II (MPS II) is a rare genetic, multiorgan disease. (bvsalud.org)
Autosomal2
- Inheritance Chong-Hai and Rajagopalan (1977) suggested autosomal recessive inheritance of pachyonychia congenita in a 4-year-old Malaysian girl with first-cousin parents, although they recognized new dominant mutation as a possibility. (findzebra.com)
- Ved autosomal recessiv (vikende) arvegang, vil en person med en sykdomsgivende forandring i ett av de to genene ikke bli syk. (frambu.no)
Growth1
- Longitudinal changes in linear growth and BMI in the mucopolysaccharidoses. (medscape.com)
Patient2
- [ 3 ] In the same year, Brailsford also reported a patient with MPS IV. (medscape.com)
- This may reflect the large amount of cold solute absorbed by the patient and confirmed by the Na measurement of 109 mEq/L. A decrease in serum Na of 20-30 mEq/L (preoperative Na was 138 mEq/L) implies absorption of 3-4 liters of fluid (dilutional hyponatremia) ( 2 ). (ispub.com)
Replacement2
- Enzyme replacement in a human model of mucopolysaccharidosis IVA in vitro and its biodistribution in the cartilage of wild type mice. (medscape.com)
- Replacement therapy in mucopolysaccharidosis type VI: advantages of early onset of therapy. (ac.ir)
Diagnosis2
- Annabelle was only 4 months old when we started the diagnosis process and two months later we got the final diagnosis which turned our lives over forever. (mpssociety.org)
- Differential Diagnosis Table 4. (symptoma.com)
Types2
- Pompe, Gaucher, Fabry, Mucopolysaccharidosis Types I, II and IV - when you type these words on your computer keyboard, you will see a bundle of red lines under them. (scmp.com)
- The physical features of MPS III are less pronounced than those of other types of mucopolysaccharidosis. (medlineplus.gov)
Typically1
- Odontoid hypoplasia can lead to misalignment of the cervical vertebrae, which may compress and damage the spinal cord, resulting in paralysis or death.In people with MPS IV, the clear covering of the eye (cornea) typically becomes cloudy, which can cause vision loss. (healthviber.com)
Children5
- If both parents carry a nonworking copy of a gene related to this condition, each of their children has a 25% (1 in 4) chance of developing the disease. (medlineplus.gov)
- Genetic counseling is recommended for couples who want to have children and who have a family history of MPS IV. (medlineplus.gov)
- Perenc L. Anthropometric characteristics of four Polish children with mucopolysaccharidosis. (medscape.com)
- The management of children with mucopolysaccharidosis (MPS) is a challenge for the anesthesiologist, primarily because of difficult airways. (ispub.com)
- Standalone cranio-cervical decompression is feasible in children with mucopolysaccharidosis type I, IVA and VI. (ac.ir)
Treatment1
- Mucopolysaccharidosis I: management and treatment guidelines. (medicalhomeportal.org)
Human2
- Hamano K, Hayashi M, Shioda K, Fukatsu R, Mizutani S. Mechanisms of neurodegeneration in mucopolysaccharidoses II and IIIB: analysis of human brain tissue. (medscape.com)
- Human ortholog(s) of this gene implicated in mucopolysaccharidosis IVA. (mcw.edu)
Tissue1
- When uninflamed, they are characterized by a wall of relatively loose connective tissue, and an epithelial lining consisting of two to four layers of cuboidal cells. (bvsalud.org)
Common1
- The purpose of this work is to report four cases, which have in common a transient hydrops fetalis, normal appearance in the postnatal period and progressive deterioration with time. (biomedcentral.com)
People3
- People with MPS IV often have joints that are loose and very flexible (hypermobile), but they may also have restricted movement in certain joints. (healthviber.com)
- The airway may become narrow in some people with MPS IV, leading to frequent upper respiratory infections and short pauses in breathing during sleep (sleep apnea). (healthviber.com)
- People with mucopolysaccharidosis (MPS) often experience a peculiar anomaly: a striking change in their bone structure. (localquoter.net)