Menkes Kinky Hair Syndrome
Loose Anagen Hair Syndrome
Brain Diseases, Metabolic
Hair
Cation Transport Proteins
Hair Follicle
Copper
Hair Cells, Auditory
Sodium arsenite enhances copper accumulation in human lung adenocarcinoma cells. (1/153)
In this report, we found that arsenite-resistant human lung adenocarcinoma cells, CL3R15, were more susceptible to CuCl2 than the parental CL3 cells. With the aid of atomic absorption spectrophotometry, we observed that CL3R15 cells accumulated more copper than CL3 cells. We further demonstrated that sodium arsenite treatment resulted in a dose-dependent increase of copper accumulation in the parental CL3 cells. In contrast, copper did not alter the levels of intracellular arsenite in CL3 cells treated in combination with sodium arsenite and CuCl2. Pretreatment of CL3 cells with sodium arsenite resulted in a significant increase of copper accumulation and cytotoxicity. These results indicate that intracellular copper accumulation is enhanced by arsenite. However, arsenite-enhanced copper accumulation was not observed in two fibroblastic cells, GM00220 and GM03700, derived from Menkes patients. The Menkes gene encodes a membrane pump responsible for copper exportation. Our results suggest that Menkes protein is a potential target of arsenite. (+info)Identification of a di-leucine motif within the C terminus domain of the Menkes disease protein that mediates endocytosis from the plasma membrane. (2/153)
The protein encoded by the Menkes disease gene (MNK) is localised to the Golgi apparatus and cycles between the trans-Golgi network and the plasma membrane in cultured cells on addition and removal of copper to the growth medium. This suggests that MNK protein contains active signals that are involved in the retention of the protein to the trans-Golgi network and retrieval of the protein from the plasma membrane. Previous studies have identified a signal involved in Golgi retention within transmembrane domain 3 of MNK. To identify a motif sufficient for retrieval of MNK from the plasma membrane, we analysed the cytoplasmic domain, downstream of transmembrane domain 7 and 8. Chimeric constructs containing this cytoplasmic domain fused to the reporter molecule CD8 localised the retrieval signal(s) to 62 amino acids at the C terminus. Further studies were performed on putative internalisation motifs, using site-directed mutagenesis, protein expression, chemical treatment and immunofluorescence. We observed that a di-leucine motif (L1487L1488) was essential for rapid internalisation of chimeric CD8 proteins and the full-length Menkes cDNA from the plasma membrane. We suggest that this motif mediates the retrieval of MNK from the plasma membrane into the endocytic pathway, via the recycling endosomes, but is not sufficient on its own to return the protein to the Golgi apparatus. These studies provide a basis with which to identify other motifs important in the sorting and delivery of MNK from the plasma membrane to the Golgi apparatus. (+info)Intracellular localization and loss of copper responsiveness of Mnk, the murine homologue of the Menkes protein, in cells from blotchy (Mo blo) and brindled (Mo br) mouse mutants. (3/153)
Menkes disease is an X-linked copper deficiency disorder that results from mutations in the ATP7A ( MNK ) gene. A wide range of disease-causing mutations within ATP7A have been described, which lead to a diversity of phenotypes exhibited by Menkes patients. The mottled locus ( Mo, Atp7a, Mnk ) represents the murine homologue of the ATP7A gene, and the mottled mutants exhibit a diversity of phenotypes similar to that observed among Menkes patients. Therefore, these mutants are valuable models for studying Menkes disease. Two of the mottled mutants are brindled and blotchy and their phenotypes resemble classical Menkes disease and occipital horn syndrome (OHS) in humans, respectively. That is, the brindled mutant and patients with classical Menkes disease are severely copper deficient and have profound neurological problems, while OHS patients and the blotchy mouse have a much milder phenotype with predominantly connective tissue defects. In this study, in an attempt to understand the basis for the brindled and blotchy phenotypes, the copper transport characteristics and intracellular distribution of the Mnk protein were assessed in cultured cells from these mutants. The results demonstrated that the abnormal copper metabolism of brindled and blotchy cells may be related to a number of factors, which include the amount of Mnk protein, the intracellular location of the protein and the ability of Mnk to redistribute in elevated copper. The data also provide evidence for a relationship between the copper transport function and copper-dependent trafficking of Mnk. (+info)A delicate balance: homeostatic control of copper uptake and distribution. (4/153)
The cellular uptake and intracellular distribution of the essential but highly toxic nutrient, copper, is a precisely orchestrated process. Copper homeostasis is coordinated by several proteins to ensure that it is delivered to specific subcellular compartments and copper-requiring proteins without releasing free copper ions that will cause damage to cellular components. Genetic studies in prokaryotic organisms and yeast have identified membrane-associated proteins that mediate the uptake or export of copper from cells. Within cells, small cytosolic proteins, called copper chaperones, have been identified that bind copper ions and deliver them to specific compartments and copper-requiring proteins. The identification of mammalian homologues of these proteins reveal a remarkable structural and functional conservation of copper metabolism between bacteria, yeast and humans. Furthermore, studies on the function and localization of the products of the Menkes and Wilson's disease genes, which are defective in patients afflicted with these diseases, have provided valuable insight into the mechanisms of copper balance and their role in maintaining appropriate copper distribution in mammals. (+info)Characterization of the Menkes protein copper-binding domains and their role in copper-induced protein relocalization. (5/153)
Menkes disease is a fatal X-linked disorder of copper metabolism. The gene defective in Menkes disease (ATP7A) encodes a copper transporting P-type ATPase (MNK or ATP7A) with six copper-binding domains at its N-terminus. MNK is normally localized to the trans -Golgi network in cultured cells, but relocates to the plasma membrane in the presence of elevated extracellular copper. In this study, the role of the six copper-binding domains on copper-induced redistribution is investigated. In a recombinant clone, when all the wild-type copper-binding motifs are mutated from GMXCXXC to GMXSXXS and the cells grown in medium containing elevated copper, relocalization of the recombinant protein to the plasma membrane was not observed. Using the same assay with any one of the six copper-binding domains intact, MNK moves to the plasma membrane in a way indistinguishable from the wild-type protein. Therefore, the copper-binding domains are vital for MNK trafficking and only a single domain is sufficient for this redistribution to occur. (+info)Defective copper-induced trafficking and localization of the Menkes protein in patients with mild and copper-treated classical Menkes disease. (6/153)
Menkes disease is an X-linked disorder of copper metabolism. An overall copper deficiency reduces the activity of copper-dependent enzymes accounting for the clinical presentation of affected individuals. The Menkes gene product (MNK) is a P-type ATPase and is considered to be the main copper efflux protein in most cells. The protein is located primarily at the trans -Golgi network (TGN), but relocalizes to the plasma membrane in elevated copper conditions to expel the excess copper from the cell. Here we report the first missense mutation which causes mild Menkes disease, a mutation in a successfully copper-treated classical Menkes patient and the effect of each mutation on the localization of MNK within the cell. Using western blot analysis, MNK was detectable in cells from both patients, but appeared to be mislocalized in the treated case. In the mild Menkes patient, the protein appeared to be located in the TGN but failed to redistribute towards the cell periphery in response to copper. This is the first description of a mutation in a Menkes patient which affects the trafficking of MNK, and the loss of this process is consistent with the clinical phenotype. (+info)Functional analysis of the N-terminal CXXC metal-binding motifs in the human Menkes copper-transporting P-type ATPase expressed in cultured mammalian cells. (7/153)
The Menkes protein (MNK) is a copper-transporting P-type ATPase, which has six highly conserved metal-binding sites, GMTCXXC, at the N terminus. The metal-binding sites may be involved in MNK trafficking and/or copper-translocating activity. In this study, we report the detailed functional analysis in mammalian cells of recombinant human MNK and its mutants with various metal-binding sites altered by site-directed mutagenesis. The results of the study, both in vitro and in vivo, provide evidence that the metal-binding sites of MNK are not essential for the ATP-dependent copper-translocating activity of MNK. Moreover, metal-binding site mutations, which resulted in a loss of ability of MNK to traffick to the plasma membrane, produced a copper hyperaccumulating phenotype. Using an in vitro vesicle assay, we demonstrated that the apparent K(m) and V(max) values for the wild type MNK and its mutants were not significantly different. The results of this study suggest that copper-translocating activity of MNK and its copper-induced relocalization to the plasma membrane represent a well coordinated copper homeostasis system. It is proposed that mutations in MNK which alter either its catalytic activity or/and ability to traffick can be the cause of Menkes disease. (+info)The Menkes protein (ATP7A; MNK) cycles via the plasma membrane both in basal and elevated extracellular copper using a C-terminal di-leucine endocytic signal. (8/153)
Menkes disease is an X-linked recessive copper deficiency disorder caused by mutations in the ATP7A ( MNK ) gene which encodes a copper transporting P-type ATPase (MNK). MNK is normally localized pre- dominantly in the trans -Golgi network (TGN); however, when cells are exposed to excessive copper it is rapidly relocalized to the plasma membrane where it functions in copper efflux. In this study, the c-myc epitope was introduced within the loop connecting the first and second transmembrane regions of MNK. This myc epitope allowed detection of the protein at the surface of living cells and provided the first experimental evidence supporting the common topological model. In cells stably expressing the tagged MNK protein (MNK-tag), extracellular antibodies were internalized to the perinuclear region, indicating that MNK-tag at the TGN constitutively cycles via the plasma membrane in basal copper conditions. Under elevated copper conditions, MNK-tag was recruited to the plasma membrane; however, internalization of MNK-tag was not inhibited and the protein continued to recycle through cyto- plasmic membrane compartments. These findings suggest that copper stimulates exocytic movement of MNK to the plasma membrane rather than reducing MNK retrieval and indicate that MNK may remove copper from the cytoplasm by transporting copper into the vesicles through which it cycles. Newly internalized MNK-tag and transferrin were found to co-localize, suggesting that MNK-tag follows a clathrin-coated pit/endosomal pathway into cells. Mutation of the di-leucine, L1487 L1488, prevented uptake of anti-myc antibodies in both basal and elevated copper conditions, thereby identifying this sequence as an endocytic signal for MNK. Analysis of the effects of the di-leucine mutation in elevated copper provided further support for copper-stimulated exocytic movement of MNK from the TGN to the plasma membrane. (+info)Menkes kinky hair syndrome, also known as Menkes disease or Steely hair syndrome, is a rare X-linked recessive genetic disorder caused by mutations in the ATP7A gene. This gene provides instructions for making a protein that plays an essential role in the body's ability to absorb and utilize copper, which is necessary for various enzymes involved in vital functions such as energy production, antioxidant activity, connective tissue synthesis, and neurotransmitter synthesis.
The main features of Menkes kinky hair syndrome include:
1. Kinky or steely hypopigmented hair: The hair is often sparse, brittle, and has a characteristic steel wool appearance due to abnormal keratin formation caused by copper deficiency.
2. Neurological symptoms: These may include developmental delays, seizures, hypotonia (low muscle tone), and progressive neurodegeneration leading to severe intellectual disability.
3. Connective tissue abnormalities: Loose skin, joint laxity, hernias, and fragile blood vessels are common features of the condition.
4. Growth failure: Affected individuals often have poor growth and weight gain.
5. Other symptoms: Menkes kinky hair syndrome can also cause gastrointestinal problems, cardiovascular issues, and temperature regulation difficulties.
The onset of symptoms typically occurs within the first few months of life, with most affected children not surviving beyond early childhood due to the severity of their neurological impairments. However, some milder forms of the disorder have been reported, which may allow for a longer lifespan and less severe symptoms.
Loose Anagen Hair Syndrome (LAHS) is a rare hair growth disorder, primarily seen in children, that is characterized by the easy and painless removal of hairs from the scalp. In this condition, the affected hairs are not firmly attached to the hair follicles, which results in increased hair shedding. The loose anagen hairs can be noticed during routine hair washing or brushing, and they often have a short, tapered root without a fully formed bulb.
LAHS is typically divided into two types:
1. **Type I (Classic)** - This form of LAHS is more common in children, particularly those under three years old. The hair growth is usually normal, but the hairs are easily extracted with minimal force. Most cases resolve spontaneously as the child grows older.
2. **Type II (Heritable)** - Also known as "Ectodermal Dysplasia Syndrome," this form of LAHS has a stronger genetic component and is often associated with other ectodermal abnormalities, such as sparse hair growth, eyebrows, or eyelashes; nail dystrophy; and dental anomalies.
The exact cause of Loose Anagen Hair Syndrome remains unclear, but it has been linked to mutations in genes responsible for the structure and function of the inner root sheath of the hair follicle. Treatment options are limited, as LAHS often resolves on its own with time. However, some cases may benefit from topical minoxidil or mild keratolytic agents to improve hair anchorage and reduce hair loss.
Metabolic brain diseases refer to a group of conditions that are caused by disruptions in the body's metabolic processes, which affect the brain. These disorders can be inherited or acquired and can result from problems with the way the body produces, breaks down, or uses energy and nutrients.
Examples of metabolic brain diseases include:
1. Mitochondrial encephalomyopathies: These are a group of genetic disorders that affect the mitochondria, which are the energy-producing structures in cells. When the mitochondria don't function properly, it can lead to muscle weakness, neurological problems, and developmental delays.
2. Leukodystrophies: These are a group of genetic disorders that affect the white matter of the brain, which is made up of nerve fibers covered in myelin, a fatty substance that insulates the fibers and helps them transmit signals. When the myelin breaks down or is not produced properly, it can lead to cognitive decline, motor problems, and other neurological symptoms.
3. Lysosomal storage disorders: These are genetic disorders that affect the lysosomes, which are structures in cells that break down waste products and recycle cellular materials. When the lysosomes don't function properly, it can lead to the accumulation of waste products in cells, including brain cells, causing damage and neurological symptoms.
4. Maple syrup urine disease: This is a genetic disorder that affects the way the body breaks down certain amino acids, leading to a buildup of toxic levels of these substances in the blood and urine. If left untreated, it can cause brain damage, developmental delays, and other neurological problems.
5. Homocystinuria: This is a genetic disorder that affects the way the body processes an amino acid called methionine, leading to a buildup of homocysteine in the blood. High levels of homocysteine can cause damage to the blood vessels and lead to neurological problems, including seizures, developmental delays, and cognitive decline.
Treatment for metabolic brain diseases may involve dietary changes, supplements, medications, or other therapies aimed at managing symptoms and preventing further damage to the brain. In some cases, a stem cell transplant may be recommended as a treatment option.
Eye manifestations refer to any changes or abnormalities in the eye that can be observed or detected. These manifestations can be related to various medical conditions, diseases, or disorders affecting the eye or other parts of the body. They can include structural changes, such as swelling or bulging of the eye, as well as functional changes, such as impaired vision or sensitivity to light. Examples of eye manifestations include cataracts, glaucoma, diabetic retinopathy, macular degeneration, and uveitis.
Medically, hair is defined as a threadlike structure that grows from the follicles found in the skin of mammals. It is primarily made up of a protein called keratin and consists of three parts: the medulla (the innermost part or core), the cortex (middle layer containing keratin filaments) and the cuticle (outer layer of overlapping scales).
Hair growth occurs in cycles, with each cycle consisting of a growth phase (anagen), a transitional phase (catagen), and a resting phase (telogen). The length of hair is determined by the duration of the anagen phase.
While hair plays a crucial role in protecting the skin from external factors like UV radiation, temperature changes, and physical damage, it also serves as an essential aspect of human aesthetics and identity.
A syndrome, in medical terms, is a set of symptoms that collectively indicate or characterize a disease, disorder, or underlying pathological process. It's essentially a collection of signs and/or symptoms that frequently occur together and can suggest a particular cause or condition, even though the exact physiological mechanisms might not be fully understood.
For example, Down syndrome is characterized by specific physical features, cognitive delays, and other developmental issues resulting from an extra copy of chromosome 21. Similarly, metabolic syndromes like diabetes mellitus type 2 involve a group of risk factors such as obesity, high blood pressure, high blood sugar, and abnormal cholesterol or triglyceride levels that collectively increase the risk of heart disease, stroke, and diabetes.
It's important to note that a syndrome is not a specific diagnosis; rather, it's a pattern of symptoms that can help guide further diagnostic evaluation and management.
Cation transport proteins are a type of membrane protein that facilitate the movement of cations (positively charged ions) across biological membranes. These proteins play a crucial role in maintaining ion balance and electrical excitability within cells, as well as in various physiological processes such as nutrient uptake, waste elimination, and signal transduction.
There are several types of cation transport proteins, including:
1. Ion channels: These are specialized protein structures that form a pore or channel through the membrane, allowing ions to pass through rapidly and selectively. They can be either voltage-gated or ligand-gated, meaning they open in response to changes in electrical potential or binding of specific molecules, respectively.
2. Ion pumps: These are active transport proteins that use energy from ATP hydrolysis to move ions against their electrochemical gradient, effectively pumping them from one side of the membrane to the other. Examples include the sodium-potassium pump (Na+/K+-ATPase) and calcium pumps (Ca2+ ATPase).
3. Ion exchangers: These are antiporter proteins that facilitate the exchange of one ion for another across the membrane, maintaining electroneutrality. For example, the sodium-proton exchanger (NHE) moves a proton into the cell in exchange for a sodium ion being moved out.
4. Symporters: These are cotransporter proteins that move two or more ions together in the same direction, often coupled with the transport of a solute molecule. An example is the sodium-glucose cotransporter (SGLT), which facilitates glucose uptake into cells by coupling its movement with that of sodium ions.
Collectively, cation transport proteins help maintain ion homeostasis and contribute to various cellular functions, including electrical signaling, enzyme regulation, and metabolic processes. Dysfunction in these proteins can lead to a range of diseases, such as neurological disorders, cardiovascular disease, and kidney dysfunction.
A hair follicle is a part of the human skin from which hair grows. It is a complex organ that consists of several layers, including an outer root sheath, inner root sheath, and matrix. The hair follicle is located in the dermis, the second layer of the skin, and is surrounded by sebaceous glands and erector pili muscles.
The hair growth cycle includes three phases: anagen (growth phase), catagen (transitional phase), and telogen (resting phase). During the anagen phase, cells in the matrix divide rapidly to produce new hair fibers that grow out of the follicle. The hair fiber is made up of a protein called keratin, which also makes up the outer layers of the skin and nails.
Hair follicles are important for various biological functions, including thermoregulation, sensory perception, and social communication. They also play a role in wound healing and can serve as a source of stem cells that can differentiate into other cell types.
Copper is a chemical element with the symbol Cu (from Latin: *cuprum*) and atomic number 29. It is a soft, malleable, and ductile metal with very high thermal and electrical conductivity. Copper is found as a free element in nature, and it is also a constituent of many minerals such as chalcopyrite and bornite.
In the human body, copper is an essential trace element that plays a role in various physiological processes, including iron metabolism, energy production, antioxidant defense, and connective tissue synthesis. Copper is found in a variety of foods, such as shellfish, nuts, seeds, whole grains, and organ meats. The recommended daily intake of copper for adults is 900 micrograms (mcg) per day.
Copper deficiency can lead to anemia, neutropenia, impaired immune function, and abnormal bone development. Copper toxicity, on the other hand, can cause nausea, vomiting, abdominal pain, diarrhea, and in severe cases, liver damage and neurological symptoms. Therefore, it is important to maintain a balanced copper intake through diet and supplements if necessary.
Auditory hair cells are specialized sensory receptor cells located in the inner ear, more specifically in the organ of Corti within the cochlea. They play a crucial role in hearing by converting sound vibrations into electrical signals that can be interpreted by the brain.
These hair cells have hair-like projections called stereocilia on their apical surface, which are embedded in a gelatinous matrix. When sound waves reach the inner ear, they cause the fluid within the cochlea to move, which in turn causes the stereocilia to bend. This bending motion opens ion channels at the tips of the stereocilia, allowing positively charged ions (such as potassium) to flow into the hair cells and trigger a receptor potential.
The receptor potential then leads to the release of neurotransmitters at the base of the hair cells, which activate afferent nerve fibers that synapse with these cells. The electrical signals generated by this process are transmitted to the brain via the auditory nerve, where they are interpreted as sound.
There are two types of auditory hair cells: inner hair cells and outer hair cells. Inner hair cells are the primary sensory receptors responsible for transmitting information about sound to the brain. They make direct contact with afferent nerve fibers and are more sensitive to mechanical stimulation than outer hair cells.
Outer hair cells, on the other hand, are involved in amplifying and fine-tuning the mechanical response of the inner ear to sound. They have a unique ability to contract and relax in response to electrical signals, which allows them to adjust the stiffness of their stereocilia and enhance the sensitivity of the cochlea to different frequencies.
Damage or loss of auditory hair cells can lead to hearing impairment or deafness, as these cells cannot regenerate spontaneously in mammals. Therefore, understanding the structure and function of hair cells is essential for developing therapies aimed at treating hearing disorders.
Adenosine triphosphatases (ATPases) are a group of enzymes that catalyze the conversion of adenosine triphosphate (ATP) into adenosine diphosphate (ADP) and inorganic phosphate. This reaction releases energy, which is used to drive various cellular processes such as muscle contraction, transport of ions across membranes, and synthesis of proteins and nucleic acids.
ATPases are classified into several types based on their structure, function, and mechanism of action. Some examples include:
1. P-type ATPases: These ATPases form a phosphorylated intermediate during the reaction cycle and are involved in the transport of ions across membranes, such as the sodium-potassium pump and calcium pumps.
2. F-type ATPases: These ATPases are found in mitochondria, chloroplasts, and bacteria, and are responsible for generating a proton gradient across the membrane, which is used to synthesize ATP.
3. V-type ATPases: These ATPases are found in vacuolar membranes and endomembranes, and are involved in acidification of intracellular compartments.
4. A-type ATPases: These ATPases are found in the plasma membrane and are involved in various functions such as cell signaling and ion transport.
Overall, ATPases play a crucial role in maintaining the energy balance of cells and regulating various physiological processes.
Ceruloplasmin
List of MeSH codes (C10)
List of MeSH codes (C18)
List of MeSH codes (C17)
Sex linkage
Menkes disease
Trichorrhexis nodosa
List of skin conditions
List of MeSH codes (C16)
Copper in biology
ATP7A15
- Identification of a novel mutation in the ATP7A gene in a Korean patient with Menkes disease. (medscape.com)
- Differences in ATP7A gene expression underlie intrafamilial variability in Menkes disease/occipital horn syndrome. (medscape.com)
- Menkes syndrome is an inherited genetic disorder due to an abnormal gene, ATP7A. (epnet.com)
- The primary cause of Menkes disease is mutations in the ATP7A gene. (mentorleo.com)
- Menkes is an X-linked disease caused by disruptive mutations in the ATP7A gene, which encodes a protein that uses ATP to pump copper across cellular membranes. (plos.org)
- The hair abnormalities observed in our patient resemble those found in Menkes disease, but sequence analysis of the ATP7A gene and relevant biochemical testing showed that ATP7A wasn't involved in causing our patient's clinical features. (plos.org)
- Menkes disease is caused by a defect in the atp7a gene. (web.app)
- Atp7a is a coppertransporting ptype atpase that is defective in the copper deficiency disorder, menkes disease. (web.app)
- In the present study, we attempted to construct a drosophila model of menkes disease by rna interference rnaiinduced silencing of dmatp7, the drosophila orthologue of mammalian atp7a, in the digestive tract. (web.app)
- The study assessed the analytic validity of an ATP7A targeted next generation DNA sequencing assay as a potential newborn screen for Menkes disease, a X-linked recessive disorder of copper metabolism caused by mutations in ATP7A, an evolutionarily conserved copper-transporting ATPase. (cypriumtx.com)
- In the study, supported in part by The Menkes Foundation ( https://themenkesfoundation.org/ ) and led by Stephen G. Kaler, M.D., M.P.H., a physician-scientist in the Center for Gene Therapy in the Abigail Wexner Research Institute at Nationwide Children's Hospital, researchers blindly analyzed dried blood spots from control or Menkes disease subjects (n=22) for pathogenic variants in the copper transporter gene, ATP7A. (cypriumtx.com)
- Menkes disease is a rare X-linked recessive pediatric disease caused by gene mutations of copper transporter ATP7A. (cypriumtx.com)
- Milder versions of ATP7A mutations are associated with other conditions, including Occipital Horn Syndrome and ATP7A-related Distal Motor Neuropathy. (cypriumtx.com)
- Menkes disease is a genetic disorder resulting from a mutation in the ATP7A gene. (thedysautonomiaproject.org)
- Menkes disease results from a mutation in a gene ( ATP7A ) on the X chromosome, so its affects boys. (rickilewis.com)
Sparse5
- Symptoms include sparse and brittle hair, slow growth or failure to thrive, and seizures. (eurekalert.org)
- Figure 1 characteristics of scalp hair in menkes disease hair is sparse, short, thin, fragile, and lightcolored, and has a steelwool appearance. (web.app)
- The condition is characterized by distinctive clinical features, including sparse and depigmented hair ("kinky hair"), connective tissue problems, and severe neurological symptoms such as seizures, hypotonia, and failure to thrive. (cypriumtx.com)
- The first signs of Menkes Disease - curly, sparse, coarse, dull, and discoloured hair - usually first develop at 2-3 months of age and therefore monitoring copper levels in babies is a way to catch this rare condition at the earliest possible opportunity. (randox.com)
- Boys have sparse, pale, and twisty hairs. (rickilewis.com)
Abnormalities9
- Oshio T, Hino M, Kirino A, Matsumura C, Fukuda K. Urologic abnormalities in Menkes' kinky hair disease: report of three cases. (medscape.com)
- Occipital horn syndrome (OHS) is a rare connective tissue disorder characterized by hyperelastic and bruisable skin, hernias, bladder diverticula, hyperextensible joints, varicosities, and multiple skeletal abnormalities. (beds.ac.uk)
- Image of wild-type (left) and littermate Hephl1 knockout (right) mice, with an insert showing hair abnormalities in a patient with biallelic HEPHL1 variants. (plos.org)
- The loss of HEPHL1 function observed in the boy and in mice leads to abnormalities in the structure of hair, strongly suggesting that the function of the multi-copper oxidase enzyme encoded by this gene is important for proper hair development and growth. (plos.org)
- How the copper deficiency in Menkes disease patients leads to hair abnormalities is not completely understood, but it has been suggested that the low activity of the enzyme sulfhydryl oxidase (which depends on copper for its activity) results in fewer of the disulfide bridges that provide structural strength and elasticity in hair [3]. (plos.org)
- Previous neuroimaging reports of patients with menkes disease describe a range of abnormalities, including intracranial vessel tortuosity and cerebral white matter changes. (web.app)
- [ 3 , 4 ] Their original classification system stratified the ectodermal dysplasias into different subgroups according to the presence or absence of (1) hair anomalies or trichodysplasias, (2) dental abnormalities, (3) nail abnormalities or onychodysplasias, and (4) eccrine gland dysfunction or dyshidrosis. (medscape.com)
- Syndromic diarrhea - Phenotypic diarrhea - Tricho-hepato-enteric syndrome - Intractable diarrhea of infancy with facial dysmorphism - Trichorrhexis nodosa and cirrhosis - Neonatal hemochromatosis phenotype with intractable diarrhea and hair abnormalities - Intractable infant diarrhea associated with phenotypic abnormalities and immune deficiency. (biomedcentral.com)
- Syndromic diarrhea (SD), also known as Phenotypic diarrhea (PD) or Tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset severe intractable diarrhea in infants born Small for Gestational Age (SGA) and associated with non-specific villous atrophy with low or no mononuclear cell infiltration of the lamina propria nor specific histological abnormalities involving the epithelium. (biomedcentral.com)
Children with Menkes2
- Children with Menkes are often born prematurely. (epnet.com)
- Children with Menkes typically have a life expectancy of less than 10 years. (thedysautonomiaproject.org)
Occipital4
- There's also a condition called the Occipital Horn Syndrome (sometimes called X-linked cutis laxa or Ehlers-Danlos type 9) which is a mild form of Menkes syndrome that begins in early to middle childhood. (smartspeechtherapy.com)
- It is characterized by calcium deposits in a bone at the base of the skull (occipital bone), coarse hair, and loose skin and joints. (smartspeechtherapy.com)
- Wilson disease, menkes disease, occipital horn syndrome, and xlinked distal hereditary motor neuropathy are genetic disorders of copper metabolism that span a broad spectrum of neurological dysfunction table 180. (web.app)
- Occipital horn syndrome is a milder allelic variant of Menkes disease. (westernindiajournal.in)
Metabolism8
- Menkes kinky hair syndrome is an X-linked recessive multisystemic lethal disorder of copper metabolism. (medscape.com)
- Menkes disease is a rare multisystem X-linked disorder of copper metabolism. (nih.gov)
- In humans, genetic disorders of Cu metabolism may cause either severe Cu deficiency (Menkes disease) or excessive Cu accumulation (Wilson disease) in the brain tissue. (johnshopkins.edu)
- Defect of copper metabolism menkes kinky hair syndrome results from head injuries, hypoxemia may worsen dyspnea increased susceptibility to infection adenitis. (albionfoundation.org)
- Menkes disease, also known as Menkes syndrome or kinky hair disease, is a rare genetic disorder that affects the absorption and metabolism of copper in the body. (mentorleo.com)
- Menkes disease is a rare genetic disorder that affects the metabolism of copper in the body. (mentorleo.com)
- Menkes disease is a genetic disorder that primarily affects the nervous system and copper metabolism. (mentorleo.com)
- New York, NY, July 29, 2020 - Fortress Biotech, Inc. (Nasdaq: FBIO) ("Fortress"), an innovative biopharmaceutical company focused on acquiring, developing and commercializing high-potential marketed pharmaceutical products and development-stage pharmaceutical product candidates, today announced the publication of a study, "Targeted Next Generation Sequencing for Newborn Screening of Menkes Disease" in Molecular Genetics and Metabolism Reports. (cypriumtx.com)
Steely Hair Disease1
- Menkes Syndrome (MNK) , also known as Menkes disease, copper transport disease , steely hair disease , kinky hair disease , or Menkes kinky hair syndrome , is a disorder originally described by John Hans Menkes (1928-2008), which affects copper levels in the body, leading to copper deficiency. (smartspeechtherapy.com)
Symptoms10
- Symptoms of Menkes kinky hair syndrome are noted within the patient's first few months of life. (medscape.com)
- The introduction of an article on Menkes disease would typically provide a brief overview of the condition, such as its definition, incidence and inheritance patterns and symptoms. (mentorleo.com)
- A deficiency of copper disrupts the normal function of enzymes and leads to the characteristic symptoms of Menkes disease. (mentorleo.com)
- The symptoms of Menkes disease typically appear within the first three months of life and can vary widely among affected individuals. (mentorleo.com)
- One of the most common symptoms of Menkes disease is delayed development. (mentorleo.com)
- Symptoms: kinky hair, mental retardation, and low copper level in the blood and a failure to synthesize the enzymes that require copper. (tjclark.com)
- In menkes disease, which is a copper deficiency disorder, many of the biochemical and clinical symptoms are attributable to reduced levels of critical copperrequiring enzymes. (web.app)
- The report covers the descriptive overview of Menkes Disease, explaining its etiology, signs and symptoms, pathophysiology, genetic basis, and currently available therapies. (westernindiajournal.in)
- Symptoms of Menkes disease begin shortly after birth and may vary from person to person. (westernindiajournal.in)
- The typical symptoms usually start by two months with characteristic skin and hair findings. (westernindiajournal.in)
Gene4
- [ 5 ] The gene locus for Menkes kinky hair syndrome is in band Xq13.3. (medscape.com)
- In the featured article [2] of the May issue of PLOS Genetics , we were able to connect the finding of anomalous hair in a young boy to a particular gene ( HEPHL1 ), and we confirmed this connection by showing that mice lacking this gene grow the curly, kinked whiskers shown in the image above. (plos.org)
- The Menkes' gene codes for a P-type ATPase that has a mutation that prevents copper absorption in the intestine. (tjclark.com)
- and (3) Rapp-Hodgkin syndrome, all of which are caused by mutations in the TP63 gene. (medscape.com)
Pili torti5
- Carrier female patients may have only a hair-shaft abnormality (ie, pili torti). (medscape.com)
- Copper-dependent metalloenzymes relevant to the clinical phenotype include tyrosinase (pigmentation of skin and hair), lysyl oxidase (elastin and collagen cross-linking), ascorbate oxidase (skeletal development), monoamine oxidase (possibly responsible for pili torti), superoxide dismutase (free-radical detoxification), dopamine beta-hydroxylase (catecholamine production), peptidyl-glycine alpha-amidating mono-oxygenase (bioactivation of peptide hormones), and cytochrome c oxidase (electron transport and possibly responsible for hypothermia). (medscape.com)
- Light microscopy shows hairs with pili torti that twist along the longitudinal axis. (medscape.com)
- Through the NIH Undiagnosed Diseases program, we evaluated a patient who presented clinically with abnormal hair ( pili torti and trichorrhexis nodosa ) and cognitive dysfunction. (plos.org)
- Microscopic analysis of the hair show twisted hair (pili torti), aniso- and poilkilotrichosis, and trichorrhexis nodosa. (biomedcentral.com)
Genetic disorder2
- Babies with Menkes syndrome have a genetic disorder that prevents the absorption of copper from the intestines. (epnet.com)
- Assuming that human milk may contain lmw copper as well as zinc complexes, williams et al 5 have suggested that human milk may also be of therapeutic value in the treatment of menkes kinky hair disease, a sexlinked genetic disorder in humans that is manifested by abnormal intestinal copper absorption and many characteristics similar to those. (web.app)
Related to copper deficiency1
- Gohil's lab identified that an experimental pharmaceutical compound, Elesclomol, could be used to improve copper levels in critical organs such as the brain and could offer a potential treatment for diseases related to copper deficiency, like Menkes disease. (eurekalert.org)
Deficiency11
- In Menkes kinky hair syndrome, a defect in intestinal copper transport with associated low serum copper and ceruloplasmin levels results in a deficiency in copper-dependent enzyme activity. (medscape.com)
- Menkes disease (Menkes kinky hair syndrome) (rare - UK incidence 1/100,000) Copper deficiency Aceruloplasminemia Zinc toxicity Greater-than-normal ceruloplasmin levels may indicate or be noticed in: copper toxicity / zinc deficiency pregnancy oral contraceptive pill use lymphoma acute and chronic inflammation (it is an acute-phase reactant) rheumatoid arthritis Angina Alzheimer's disease Schizophrenia Obsessive-compulsive disorder Normal blood concentration of ceruloplasmin in humans is 20-50 mg/dL. (wikipedia.org)
- Menkes disease (MNK) is an X-linked recessive disorder characterized by generalized copper deficiency. (beds.ac.uk)
- Arsenic deficiency in humans results in a "carpal tunnel syndrome," "TMJ," and other "repetitive motion" type degeneration. (mighty-90.com)
- Dryness may also result from sebum deficiency on the hair surface because of absence or decrease in sebaceous gland secretions. (visualstories.com)
- A deficiency of copper in the liver and other tissues is the primary cause of Menkes disease. (mentorleo.com)
- As a result, copper accumulates in the liver, while other tissues and organs, especially the brain and the hair follicles, suffer from a severe deficiency of copper. (mentorleo.com)
- Menkes' disease results in pathology resembling copper-deficiency, as opposed to the pathology of Wilson's disease, which resembles copper-toxicity. (tjclark.com)
- Menkes' syndrome is a hereditary disorder causing copper deficiency. (tjclark.com)
- Menkes disease (MNK), also known as Menkes syndrome, is a X-linked recessive disorder that affects copper levels in the body, leading to copper deficiency. (icd.codes)
- Copper deficiency can also be caused by an inherited disorder called Menkes Disease. (randox.com)
Disorders4
- Dry hair can be a symptom of certain metabolic disorders such as Menkes kinky hair syndrome and hypothyroidism. (visualstories.com)
- Marfan syndrome, cutis laxa, mitochondrial disorders, osteogenesis imperfecta and child abuse, may also need to be ruled out when making a differential diagnosis. (smartspeechtherapy.com)
- Overview of Malabsorption Malabsorption syndrome refers to a number of disorders in which nutrients from food are not absorbed properly in the small intestine. (msdmanuals.com)
- In 1962 menkes et tablished a new syndrome among the numerous neurodegenerative disorders of early childhood. (web.app)
Recessive4
- A sex-linked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. (medscape.com)
- Autosomal recessive keratitis-ichthyosis-deafness syndrome (KIDAR) is characterized by neonatal-onset ichthyotic erythroderma and profound sensorineural deafness, with failure to thrive and developmental delay in childhood. (beds.ac.uk)
- Menkes disease is inherited in an X-linked recessive pattern. (mentorleo.com)
- The most common ectodermal dysplasias are X-linked recessive hypohidrotic ectodermal dysplasia (Christ-Siemens-Touraine syndrome), as shown in the image below, and hidrotic ectodermal dysplasia (Clouston syndrome). (medscape.com)
Scalp hair1
- Anagen lasts up to 6 years or longer in scalp hair. (dermnetnz.org)
Connective-tissue4
- The clinical phenotype is marked by fine silvery wiry hair, doughy skin, connective-tissue disturbances, and progressive neurologic deterioration. (medscape.com)
- Copper is an essential mineral that is needed for the normal function of several enzymes and is involved in the development of connective tissue, the production of melanin (a pigment that gives color to the skin, hair, and eyes), and the absorption of iron. (mentorleo.com)
- Copper is an essential mineral that plays a vital role in many physiological processes, including the formation of connective tissue, the production of melanin (the pigment that gives color to the skin and hair), the absorption and transport of iron, and the activity of enzymes involved in energy production and antioxidant defense. (mentorleo.com)
- One of the best known of these is Menkes kinky hair syndrome, which is characterized by the presence of a peculiar "kinky hair" trait and degeneration of the brain, bones and connective tissue. (plos.org)
Biochemical2
- The results of our study support proof-of-concept that primary DNA-based NBS would accurately detect Menkes disease, a disorder for which biochemical detection in the newborn period is currently unavailable. (cypriumtx.com)
- These non-specific clinical and biochemical findings could result in the misdiagnosis of neonatal Menkes disease. (westernindiajournal.in)
Absorption4
- Menkes syndrome causes impaired copper absorption. (epnet.com)
- Menkes disease is an inherited, fatal pediatric disease caused by impaired absorption and distribution of dietary copper in the body. (eurekalert.org)
- Menkes' kinky-hair disease is a problem with copper transport or absorption. (tjclark.com)
- The less buzzy, but more classic strategy of providing a nutrient that a genetic glitch blocks, has been quietly making strides against Menkes disease, which impairs copper absorption. (rickilewis.com)
Phenotype2
- The phenotype of Menkes kinky hair syndrome is manifest in male patients. (medscape.com)
- The phenotype of the rats starved for copper seems to mimic as regards pigmentation the phenotype of the mouse Mo (mottled) mutation that is an experimental model of the Menkes' kinky hair syndrome. (unicatt.it)
Deterioration3
- Progressive neurologic deterioration occurs in persons with Menkes kinky hair syndrome. (medscape.com)
- Characteristic findings of the disorder include kinky hair, growth failure, and nervous system deterioration. (carolhenshaw.com)
- MNK is characterized by kinky hair, growth failure, and deterioration of the nervous system. (icd.codes)
Typically1
- The onset of Menkes disease typically begins during infancy, affecting about 1 in 100,000 to 250,000 newborns. (icd.codes)
Lethal2
- Pdf menkes disease is an xlinked lethal multisystem disorder caused by the disturbances of copper distribution in different tissues due to the. (web.app)
- Menkes disease is a lethal infantile neurodegenerative disorder with X-linked inheritance. (westernindiajournal.in)
Prognosis2
- The prognosis for Menkes kinky hair syndrome is poor. (medscape.com)
- Prognosis of this syndrome is poor, but most patients now survive, and about half of the patients may be weaned from PN at adolescence, but experience failure to thrive and final short stature. (biomedcentral.com)
Hereditary1
- Sometimes FD is referred to as Riley-Day syndrome or type III hereditary sensory and autonomic neuropathy (HSAN type III). (thedysautonomiaproject.org)
Neurodegenerative disorder1
- Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. (web.app)
Epidemiology2
- DelveInsight's 'Menkes Disease Market Insights, Epidemiology, and Market Forecast-2032' report deliver an in-depth understanding of the Menkes Disease, historical and forecasted epidemiology as well as the Menkes Disease market trends in the G11 i.e. (westernindiajournal.in)
- Comprehensive insight has been provided into Menkes Disease epidemiology and treatment. (westernindiajournal.in)
Neurological1
- Neurological manifestations are the most common and characteristic of Menkes disease. (westernindiajournal.in)
Follicles3
- The tissues primarily involved are the skin and its appendages (hair follicles, eccrine glands, sebaceous glands, and, nails) and teeth. (medscape.com)
- As all our hair follicles are formed during fetal growth, it is inevitable that we will notice hair loss of some kind in later life. (dermnetnz.org)
- Short broken hairs and empty follicles may be observed. (dermnetnz.org)
Severe3
- Huppke-Brendel syndrome (HBS) is characterized by bilateral congenital cataracts, sensorineural hearing loss, and severe developmental delay. (beds.ac.uk)
- You may also suffer from severe hair loss. (visualstories.com)
- Syndromic diarrhea (SD), also known as phenotypic diarrhea (PD) or tricho-hepato-enteric syndrome (THE), is a congenital enteropathy presenting with early-onset of severe diarrhea requiring parenteral nutrition (PN). (biomedcentral.com)
Copper transport2
- In Menkes kinky hair syndrome, intestinal copper uptake by brush border cells is normal, but copper transport to other tissues is affected. (medscape.com)
- Correction of the copper transport defect of menkes. (web.app)
Findings1
- Joshi P, Lele V, Gandhi R . Fluorodeoxyglucose positron emission tomography-computed tomography scan and nuclear magnetic resonance findings in a case of Stewart-Treves syndrome. (bankersvascular.com)
Male infant1
- Classic menkes kinky hair disease in an 8-month-old male infant. (medscape.com)
Phenotypic1
- Phenotypic convergence of menkes and wilson disease. (web.app)
Treatment6
- The currently enriched knowledge of neuroradiologic finding evolution provides valuable clues for early diagnosis, identifies possible MR imaging biomarkers of new treatment efficacy, and improves our comprehension of possible mechanisms of brain injury in Menkes disease. (nih.gov)
- Under their license agreement, Engrail now leads development of a complex of Elesclomol-copper for the treatment of Menkes disease, while AgriLife Research continues conducting preclinical research through a sponsored research grant. (eurekalert.org)
- NBS could potentially increase the number of Menkes disease patients identified at birth allowing for earlier treatment, a critical component correlated with clinical outcome. (cypriumtx.com)
- The Menkes Disease market report provides current treatment practices, emerging drugs, market share of individual therapies, and current and forecasted G11 Menkes Disease market size from 2019 to 2032. (westernindiajournal.in)
- The Report also covers current Menkes Disease treatment practice, market drivers, market barriers, SWOT analysis, reimbursement, market access, and unmet medical needs to curate the best of the opportunities and assesses the underlying potential of the market. (westernindiajournal.in)
- Additionally, an all-inclusive account of both the current and emerging therapies for Menkes Disease is provided, along with the assessment of new therapies, which will have an impact on the current treatment landscape. (westernindiajournal.in)
Incidence2
- Considering live-born Menkes patients, the combined incidence for these five countries is 1 Menkes patient per 298,000 live-born babies. (westernindiajournal.in)
- If the number of affected aborted fetuses is taken into account, the incidence is 1 Menkes per 254,000 live-born babies. (westernindiajournal.in)
Pigmentation1
- The mineral is also essential for hair growth and pigmentation, which is why Menkes is also called kinky hair disease. (rickilewis.com)
Abnormal1
- Biochemically, Menkes patients have low levels of copper in their blood and brain, as well as abnormal levels of certain neurochemicals. (cypriumtx.com)
Newborn1
- A newborn boy with anhidrotic/hypohidrotic ectodermal dysplasia syndrome showing generalized fine scaling and a history of intermittent fever. (medscape.com)
Infants2
- Targeted next generation sequencing for NBS would enable improved Menkes disease clinical outcomes through early detection, and eliminate the lengthy, expensive, and uncomfortable diagnostic odysseys endured by many affected infants and their parents," said Dr. Kaler, who is also a professor of Pediatrics and Genetics at The Ohio State University College of Medicine. (cypriumtx.com)
- Infants with MNK syndrome often do not live past the age of 3. (icd.codes)
Peculiar hair1
- Children with MNK have strikingly peculiar hair, which is kinky, colorless or steel-colored, and easily broken. (smartspeechtherapy.com)
Cerebral1
- Cerebral infarction in menkes disease pediatric neurology. (web.app)
