Menkes disease is caused by a defect in the atp7a gene. Disorders of copper homeostasis are currently recognized across. If you have problems viewing pdf files, download the latest version of adobe reader. Several mutations in the atp7a gene are responsible for a condition called occipital horn syndrome or xlinked cutis laxa, which is considered a mild form of menkes syndrome.
Isolation of a candidate gene for menkes disease and evidence that it encodes a coppertransporting atpase. Following the german annexation of austria, menkes immigrated to the united states with his family in 1939 at the age of 11 years. Onset of menkes syndrome typically begins during infancy. Clinical expression of menkes disease in females with.
Menkes syndrome is usually inherited, which means it. A cellpermeable gadolinium contrast agent for magnetic. Hence, prudence is advised in always ruling out nat, particularly when other intracranial signs of menkes disease are not seen. Menkes disease kinky hair disease, steely hair disease, trichopoliodystrophy. Clinical expression of menkes disease in females with normal. Media in category menkes disease the following 8 files are in this category, out of 8 total. The diagnosis was made on the combination of clinical features with laboratory and radiological findings. Radiological findings in a case of menkes disease springerlink.
Menkes disease, national institute of neurological diseases and stroke ninds menkes disease, online mendelian inheritance of man omim menkes syndrome, medicinenet. Progressive neurodegeneration and connective tissue disturbances. Menkes disease may mimic nonaccidental trauma with retinal hemorrhage and bilateral subdural hematomas. Occipital horn syndrome is one of the less severe forms of menkes syndrome that begins in early to middle childhood. Menkes syndrome additional clinical hair is fuzzy and palpably dry.
Occipital horn syndrome and a mild menkes phenotype associated with splice site mutations at. Like all xlinked recessive conditions, menkes disease is more common in males than in females. Occipital horn syndrome and a mild menkes phenotype associated with splice site mutations at the mnk locus. Discussion menkes disease is a broad range of conditions that affects males xlinked. Causes menkes disease is caused by a defect in the atp7a gene. In females who have two x chromosomes, a mutation would have to occur in both copies. Much noise has been made in the popular media about the role of metals in health. Partial gene duplications in atp7a accounts for 5% of the disease causing mutations in menkes disease.
Menkes disease is a rare, often fatal neurodegenerative disease that affects the bodys ability to absorb copper. We describe a 7 months male patient who presented with seizures, hypoactivity and absence of visual contact. Pili torti is usually present in all patients within the spectrum. Menkes disease is an inherited disorder in which the body has a problem absorbing copper. Milder variants of menkes disease, including occipital horn syndrome also known as xlinked cutis laxa or ehlersdanlos type 9 have also been described. Porterfield will be contributing a post on the menkes syndrome. The frequency of wilsons disease in most populations is about 1 in 30,00040,000, and the frequency of carriers of atp7b mutations is. Clinical diagnosis can be confirmed by quantifying serum and urinary levels of copper, serum ceruloplasmin level and genetic study 5. Because of the severity of the prognosis and in order to plan treatment, the correct diagnosis has to be. Menkes disease md mim 309400 is a rare xlinked recessive disorder, with an incidence of about 1.
A mild form of menkes disease was originally reported in 1981 and clinical progress of the patient at 10 years described subsequently. This gene encodes a copper transporting ptype atpase, essential for the release of dietary copper from the intestine to the body, including the brain. Pdf menkes disease is an xlinked lethal multisystem disorder caused by the disturbances of copper distribution in different tissues due to the. A number of other eponyms, such as menkes steely hair disease, menkes kinky hair disease, trichopoliodystrophy, and menkes syndrome, have. Menkes disease is the result of defects in the ptype atpase protein that is responsible for the translocation of copper across the intestinal basolateral membrane into the. On the basis of longitudinal followup, patients were classified as affected or unaffected by menkes disease, and the neurochemical pro files were shown to have. Also known as kinky hair syndrome and copper transport disease. Xlinked means that the gene for the condition is located on the xchromosome, one of the sex chromosomes. Characteristic findings include kinky hair, growth failure, and nervous system deterioration. The university of chicago genetic services laboratories. Menkes disease mnk, also known as menkes syndrome, is an xlinked recessive disorder caused by mutations in genes coding for the coppertransport protein atp7a, leading to copper deficiency. According to the current literature, the most frequent.
Menkes disease is so named because it was originally described in 1962 by dr. The occipital horn syndrome is caused by mutation in the same gene. Infants will lose, or fail to demonstrate, specific developmental milestones and failure to thrive. Abstract menkes disease is a rare xlinked disorder related to a defect in the copper metabolism. Menkes disease is a rare xlinked recessive disorder of copper metabolism. Mar 27, 2019 menkes disease is caused by a defective gene named atpta 1 that regulates the metabolism of copper in the body. We report on two cases of classical menkes disease with typical history, progressive psychomotor deterioration. Menkes disease genetic and rare diseases information. Progressive neurodegeneration and connective tissue disturbances, together with. Females are carriers of menkes syndrome, and their sons who have the gene have the disease. Menkes syndrome is a disorder that affects copper levels in the body. Swartz5 menkes kinkyhair disease trichopoliodystrophy, steely hair disease is an xlinked neurodegenerative disorder that occurs predominantly in males. But just as it is important to avoid some metals, others are absolutely required for. As a result, the brain and other parts of the body do not get enough copper, while it builds up in the small intestine and kidneys.
A collection of disease information resources and questions answered by our genetic and rare diseases information specialists for menkes disease. This kind of gene inheritance is called xlinked recessive. Learn about the origins of the disease, plus symptoms, diagnosis, and treatment options. Classical menkes disease is a neurodegenerative disorder caused by mutations in the coppertransporting atpase atp7a gene which, when untreated, is usually fatal in early childhood. Inevitably, the biggest stories revolve around poisonings that result from metal overloadwhether from leadbased paints, mercuryfilled thermometers see this issues for your health, or arsenicbased poisons. The distinctive clinical features of menkes disease are usually present by 3 months of age. The pathogenesis of the skeletal findings in menkes disease is as yet unclear. Menkes disease, copper metabolism, epilepsy, pili torti, cerebral degeneration introduction menkes disease md, also referred to as kinky hair disease, trichopoliodystrophy, and steely hair disease, is a rare xlinked recessive disorder of copper metabolism. Menkes disease genetic and rare diseases information center. Menkes syndrome is inherited in an xlinked recessive pattern. Menkes disease is named after the american physician john h menkes 19282008 7. An slps perspective on menkes syndrome earn 10 reward points by commenting the blog post november is menkes awareness month, so today olga z. Menkes disease also called the kinky hair disease or menkes kinky hair syndrome is a disorder that affects copper levels in the body.
A sexlinked recessive disorder with retardation of growth, peculiar hair, and focal cerebral and cerebellar degeneration. Jan 22, 2012 menkes disease md mim 309400 is a rare xlinked recessive disorder, with an incidence of about 1. Researchers have identified more than 150 mutations in the atp7a gene that cause menkes syndrome. The documents contained in this web site are presented for information. Carrier females do not typically have symptoms, but 50% have been reported to have patches of pili torti. Some patients exhibit mild menkes disease with severity in the middle of this spectrum. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar kinky hair are the main manifestations. Pmc free article vulpe c, levinson b, whitney s, packman s, gitschier j. Menkes diseasea hypothesis with recommandations for. Menkes disease mnk, also known as menkes syndrome, is an xlinked recessive disorder caused by mutations in genes coding for the coppertransport. Menkes disease is a disorder that affects copper levels in the body.
Recent research in menkes disease has focused on a defective copper metabolism. Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a copper transport protein. Xlinked means that the gene for the condition is located on the x chromosome, one of the sex chromosomes. Menkes disease md is a usually severe multisystemic disorder of copper. Progressive neurodegeneration and connective tissue. Dec 10, 2019 a girl with the menkes disease phenotype and an x. If the disorder is recognized early, injections of copper have been sometimes beneficial. This means that menkes disease, or a subtype of menkes disease, affects less than 200,000 people in the us population. Menkes disease or kinky hair syndrome is a multisystemic disorder with an x linked inheritance, and mutation of the gene atp7a located on xq.
Some additional signs and symptoms may include weak muscle tone hypotonia, sagging facial features, seizures, developmental delay, and intellectual disability. The menkes disease gene is atp7a encodes an enzyme p type atpase which is required for systemic absorbtion, distribution and metabolism of copper in tissues. In females who have two x chromosomes, an alteration needs to occur in both. Menkes disease md is a degenerative disease, with an xlinked recessive inheritance, characterized by involvement of the nervous system due to an intracellular defect of the copper transport protein 15. Like all xlinked recessive conditions, menkes disease is.
The clinical spectrum of menkes disease includes progressive neurodegeneration, connective tissue abnormalities and wiry brittle hair. 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 19282008, which affects copper levels in the body, leading to copper. Menkes disease, a neurodegenerative progressive xlinked disorder, was diagnosed in a 4monthold child. Many of these mutations delete part of the gene and likely result in a shortened atp7a protein.
Menkes disease nord national organization for rare disorders. Light microscopic examination of the hair demonstrated the pili torti pattern. Copper accumulates at abnormally low levels in the liver and brain, but at higher than normal levels in. Occipital horn syndrome is characterized by loose and sagging skin, wedgeshaped calcium deposits in a bone at the base of the skull the occipital bone, coarse hair, and loose joints. Menkes disease md is an inherited xlinked recessive disorder that affects many systems in the body. We report on two cases of classical menkes disease with typical history, progressive psychomotor deterioration and seizures, clinical manifestations cherubic appearance, with brittle, scattered and hypopigmented scalp hairs, and progression. The disease affects development, both mental and physical. Menkes disease information page national institute of. Since the ys cells are lacking a copper export system they can serve as a model for wd. Menkes disease symptoms, diagnosis, treatments and causes. Cells were exposed to copper under conditions representing acute and chronic copper overload.
Menkes disease md is a rare xlinked recessive fatal neurodegenerative disorder caused by mutations in the atp7a gene, and most patients. The defect makes it hard for the body to properly distribute transport copper throughout the body. The cellular redox status is altered in menkes disease. Copper accumulates at abnormally low levels in the liver and brain, but at higher than normal levels in the kidney and intestinal lining. It is characterized by progressive cerebral degeneration with psychomotor deterioration, hypothermia, seizures and characteristic facial appearance with hair abnormalities. Md is inherited as an xlinked recessive trait, and as expected the vast majority of patients are males. Siblings of a diagnosed patient have a 1 in 4 risk of wilsons disease, whereas children of an affected patient have about a 1 in 200 risk. Source national institutes of health nih ophanet, a consortium of european partners, currently defines a condition rare when it affects 1 person per 2,000. In males who have only one x chromosome, one altered copy of the gene is enough to cause the condition.
The gene is on the xchromosome, so if a mother carries the defective gene, each of her sons has a 50% 1 in 2 chance of developing the disease, and 50% of her daughters will be a carrier of the disease. Menkes disease is a rare neurodegenerative disorder due to an intracellular defect of a. Affected infants are often born prematurely and may have nonspecific symptoms such as hypothermia, hypoglycemia, and prolonged jaundice. Menkes syndrome is usually inherited, which means it runs in families. Menkes disease is inherited in an xlinked recessive pattern and mainly affects boys. It is characterized by sparse and coarse hair, growth failure, and deterioration of the nervous system. Menkes disease and occipital horn syndrome testing. In males who have only one x chromosome, one altered copy of the gene in each cell is sufficient to cause the condition. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar kinky hair are the main. Recommandations for future research are given with special emphasis on the neuropathological aspects. Menkes disease md is a lethal multisystemic disorder of copper metabolism.
Additional signs and symptoms include weak muscle tone hypotonia, sagging facial features, seizures. Menkes disease, also known as trichopoliodystrophy or kinky hair kinky vessel syndrome, is an xlinked recessive disorder that results in a derangement in copper handling. Cloning of the gene defective in the xlinked neurodegenerative disorder menkes disease led to a cascade of new findings. The defect makes it hard for the body to properly distribute transport copper. Mar 30, 2020 menkes disease is inherited in an xlinked recessive pattern and mainly affects boys. November is menkes awareness month, so today olga z. Menkes diseasea hypothesis with recommandations for future investigations. John hans menkes was a pediatric neurologist, born in vienna, austria, in 1928. Other mutations insert additional dna building blocks nucleotides into the gene or change single nucleotides.
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