Menkes disease md, also known as kinky hair disease or trichopoliodystrophy or steely hair disease, is an xlinked neurodegenerative disease of abnormal copper transport, resulting in copper maldistribution and relative deficiency in tissues like serum, brain, and liver 1, 2. Because of the characteristic malformedhair foundin the syndrome, menkescalled it kinky hair disease. The gene for khd is about 200 kb in size and is located on the long arm of x chromosome xql3. Like all xlinked recessive conditions, menkes disease is. Menkes disease genetic and rare diseases information center. Pdf neonatal diagnosis and treatment of menkes disease. Many hair diseases can be associated with distinct underlying disorders. Menkes kinky hair disease mkhd or trichopoliodystrophy is a progressive neurodegenerative disorder with an incidence of 1 case per 300000 1. En arftlig, xkromosombunden storning i kopparmetabolismen. Ppt menkes disease powerpoint presentation free to.
Occipital horn syndrome and a mild menkes phenotype associated with splice site mutations at the mnk locus. Pdf correction of cerebrospinal fluid copper in menkes. Menkes kinky hair disease is a rare xlinked recessive disease nearly exclusively affecting males who present at 2. Menkes disease atpase atp7a is internalized via a rac1. A cherubic appearance and sparse brittle and colourless hair are characteristic. A second localization signal in the atp7a protein is a dileucine motif that regulates internalization at the plasma membrane and mediates endosomal targeting 12.
Menkes kinky hair syndrome menkes kinky hairsyndrom svensk definition. Correction of cerebrospinal fluid copper in menkes kinky hair disease. Characterization of atp7a missense mutants suggests a. Menkes kinky hair disease is a rare xlinked recessive disease nearly exclusively affecting males who present at 23 months of age due to abnormal functioning of copperdependent enzymes due to deficiency of copper. Immunohistochemical investigations were carried out on cerebellar purkinje cells in patients with menkes kinky hair disease md and normal control. Wray, toichiro kuwabara, and paul sanderson light and electron microscopic studies of the ocular tissue of a case of menkes kinky hair disease are described.
Menkes kinky hair disease mkhd is a rare xlinked recessive lethal. Menkes disease, copper metabolism, epilepsy, pili torti, cerebral degeneration. Here, we describe a completely workedup case of a 4monthold male infant with very typical history and radiological features confirmed by biochemical and. Unusual facial features include pudgy cheeks and abnormal eyebrows. Tillstandet kannetecknas av hypotermi redan fran barndomen, atsvarigheter, lagt blodtryck, krampanfall, benvavnadsmissbildningar, pili torti vridna har och starkt forsamrad mental utveckling. Identification of a novel mutation in the atp7a gene in a. Seventeenmonthsold saudi infant was presented with repetitive seizures and was diagnosed to have epilepsia partialis continua. They develop little or no motor skills, do not acquire language skills, and many.
The neurologic disorder was static and characterized by hypotonia and choreoathetosis. Menkes disease md is a rare xlinked recessive fatal neurodegenerative disorder caused by mutations in the atp7a gene, and most patients are males. Menkes kinky hair disease choudhary sv, gadegone rw, koley. Encyclopedia of genetics, genomics, proteomics and informatics. Brittle, kinky monamide oxidase hair on infants is short, sparse, coarse, and twisted. The most promising therapy to date, very early subcutaneous copper injections, has. However, the changes in skeletal features over time are not well known. Menkes disease or kinky hair syndrome is a multisystemic disorder with an x linked inheritance, and mutation of the gene atp7a located on xq. In 1962, a doctor named john menkes and his colleagues at columbia university in new york published a scientific article about five male infants with a distinctive genetic syndrome. Menkes disease md, also known as kinky hair disease, is a multifocal. The patient was diagnosed as menkes disease and treated symptomatically. Menkes disease genetic and rare diseases information. Additional signs and symptoms include weak muscle tone hypotonia, sagging facial features, seizures.
Menkes disease also called the kinky hair disease or menkes kinky hair syndrome is a disorder that affects copper levels in the body. A ten minute documentary on menkes disease a rare fatal genetic disorder. Kinky hair disease khd was first described by menkes et al. Menkes disease 1 menkes disease melissa apostolidis 2 aka kinky hair disease. Neuroimaging in menkes disease ahmed mi, hussain n j.
Menkes disease is an infantileonset xlinked recessive neurodegenerative disorder caused by deficiency or dysfunction of a coppertransporting atpase, atp7a. Some additional signs and symptoms may include weak muscle tone hypotonia, sagging facial features, seizures, developmental delay, and intellectual disability. Menkes disease is characterized by dry skin and abnormal hair that is often brittle, tangled, sparse, steely or kinky and is often white, ivory, or grey in color. A case report sangita ghosh mbbs ddvl, soumik chaudhuri mbbs md medicine dermatology online journal 18 11. Menkes disease an xlinked recessive condition omim. In 1962, menkes encountered a male infant who, while developmentally normal at birth, quickly developed floppy muscle tone, seizures, and coarse, brittle hair. The abnormality is a defect of transmembrane transport of copper resulting in increased copper deposition in intestine and pancreas, with copper deficiency in the brain. Recently it has been known that this disease is also characterized by multiple. The affected infant may also appear to have a yellow appearance jaundice which is caused by excessive bilirubin in the blood hyperbilirubinemia. Menkes disease is a disorder that affects copper levels in the body. Epilepsy is one of the main clinical features of this disease but it has been described in detail by only a few authors.
The characteristic clinical features are steely hair, profound retardation, spastic quadriparesis, seizures, and hypothermia. Additional signs and symptoms include weak muscle tone hypotonia, sagging facial features, seizures, developmental. Menkes disease is characterized by brittle, tangled, sparse, steely or kinky hair that is often white, ivory, or gray in color. Menkes disease, kinky hair, ceruloplasmin, neurodegenerative. Menkes disease presenting with epilepsia partialis continua. Biochemically, menkes patients have low levels of copper in their blood and brain, as well as abnormal levels of certain neurochemicals. Thoughmostpatients 9095% have a severe clinical course table 1, various forms ofthe. Menkes chief contribution to medicine was his discovery of kinky hair syndrome or menkes disease. It is caused by a mutation in the atp7a gene, which codes for the coppertransporting atpase in the cell organelles.
Clinical expression of menkes disease in females with. In the first case which documents the sexlinked recessive inheritance, arteriographic studies have shown that the vascularization of the brain was severely impaired. Sir, menkes kinky hair disease is a rare xlinked recessive disorder of copper metabolism. The cdna has been recently sequenced and is known to code. Menkes disease is a lethal multisystemic disorder of copper metabolism characterized by connective tissue abnormalities, progressive neurodegeneration and peculiar kinky hair. Menkes disease is a rare xlinked recessive pediatric disease caused by gene mutations of copper transporter atp7a, which affects approximately one in 100,000 newborns per year. Menkes syndrome is a disorder that affects copper levels in the body. Hair diseases are disorders primarily associated with the follicles of the hair.
Danks et al3 reported seven new cases of menkes kinky hair syndrome from five families seen over a period of 3 years in melbourne, australia. Differences from menkes disease included normal birth weight, no hypothermia, grossly and microscopically normal hair, and radiographically normal bones. The characteristics facies, fair complexion, chubby cheeks, sparse twisted fuzzy depigmented hair. We aim to describe a female patient with menkes disease who presented with epilepsia partialis continua. Menkes disease md is a lethal multisystemic disorder of copper metabolism. The clinical phenotype is marked by fine silvery wiry hair, doughy skin, connective tissue disturbances, and progressive neurologic deterioration. This report notes important changes in the eyes which were found on histological examination. Sep 18, 2008 menkes disease results in developmental delay, seizures, hypotonia which is more in trunkal muscle and feeding difficulties. Characteristic findings include kinky hair, growth failure, and nervous system deterioration. Immunohistochemical investigations on cerebellar purkinje. Like all xlinked recessive conditions, menkes disease is more common in males than in females.
Menkes disease nord national organization for rare. Menkes kinky hair disease is an xlinked recessive trait caused by mutations in the atp7a gene leading to disturbed copper metabolism contributing to low serum copper and ceruplasmin. Danks et al first noted that copper metabolism is abnormal in 1972. Clinical findings progressive mental deterioration, kinked or twisted brittle hair, skeletal defects, death in infancy. This disease is clinically characterized by seizures, friable hair, growth failure, mental retardation and others. Diverticula of the bladder in a boy with menkes disease. Pdf rahul ojha,1 asuri n prasad14 1department of pediatrics, 2section of. It is characterized by sparse and coarse hair, growth failure, and deterioration of the nervous system. Skeletal findings in infants with menkes disease, the most characteristic of which are metaphyseal spurs, longbone fractures and wormian bones, have been widely reported. Balding can be localised or diffuse, scarring or nonscarring. It is characterized by brittle, tangled, sparse, steely or kinky hairs that are often white, ivory, or gray in color with easy pluckability. Mr demonstrated characteristic cerebrovascular tortuousity and thus may be a.
Pdf menkes disease md is a lethal multisystemic disorder of copper metabolism. Fibroblastic cells cultured from the skin of patients and of heterozygous females show intense. In menkes kinky hair disease, intestinal copper uptake is normal, but copper transport to other tissues is affected. Menkes disease omid 309400, also known as kinky hair disease, is an infantileonset xlinked recessive neurodegenerative disorder caused by diverse mutations in a coppertransport gene, atp7a 1, 2. Menkes kinky hair syndrome, also known as trichopoliodystrophy, is a rare xlinked recessive, progressive neurodegenerative disorder characterized clinically by progressive psychomotor. Longterm skeletal findings in menkes disease springerlink. Menkes kinky hair disease is a rare xlinked recessive disorder of copper metabolism. These patients can present with failure to thrive, severe psychomotor retardation, seizures and hypopigmented hair, which is characteristic of this condition. Two cases of menkes disease belonging to different families are reported in order to illustrate different types of central nervous system involvement. The defect in copper absorption in this disease must lie in the process of intracellular handling or of transport across the serosal cell membrane. 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 deficiency. Early treatment with copper injections may prevent death and illness. Menkes disease results in developmental delay, seizures, hypotonia which is more in trunkal muscle and feeding difficulties.
Lethal neonatal menkes disease with severe vasculophaty and fractures. His hair is depigmented and lusterless with pili torti and the skin is pale with eczema. Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse mutations in a coppertransport gene, atp7a. It is an xlinked recessive disorder, and is therefore.
Menkes kinky hair syndrome is an xlinked recessive multisystemic lethal disorder of copper metabolism. Jul 01, 2003 the menkes disease protein contains eight transmembrane domains, and a specific transmembrane domain has been shown to be essential for tgn localization of atp7a. Seizures were polymorphic, combining brief tonic seizures. Full text pdf 4498k abstracts references9 menkes kinky hair disease is a poor prognostic congenital disease with xlinked recessive inheritance. I was doing some hair research on copper and health, including hair and i found this article on copper that also discussed menkes syndrome also known as kinky hair disease or menkes kinky hair syndrome. Menkes disease md, also referred to as kinky hair disease, trichopoliodystrophy, and steely hair disease, is a rare xlinked recessive disorder of copper metabolism. Atypical form of menkes kinky hair disease with mitochondrial nadhcoq reductase deficiency. Menkes disease what affect do these mutations have. Dermatologic manifestations of menkes kinky hair disease. This syndrome, now known as menkes disease, menkes kinky hair disease or menkes syndrome, has been identified as a disorder of copper metabolism in the body. Biphasic effects of copper on neurotransmission in rat. Hair disease may refer to excessive shedding or baldness or both. Abstract the importance of copper in the cns is well documented, but the mechanisms related to its brain functions are poorly understood. In the largest cohort of md patients reported so far which consists of 517 families we.
Flared metaphyses of the ulna and radius in a 5monthold patient with classic menkes disease. Menkes disease is an infantileonset xlinked recessive neurodegenerative disorder caused by deficiency or dysfunction of a coppertransporting atpase. The copper deficiency responsible for this systemic and neurologic. Manufacturing and stability of copperhistidine solution for. Microscopic examination of hair revealed pili torti. Menkes disease, 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. Kinky hair disease, also known as menkes kinky hair disease or trichopoliodystrophy, is a focal degenerative disorder of gray matter first described in 1962 by menkes et al. Menkes described a previously unrecognized entity of cerebellar and focal cerebral degeneration, with kinky hair, failure to thrive and early death occurring in boys only. Some ten years after the disease was first described, danks et al. We report two cases of menkes kinky hair disease in which mr and mr angiography were performed. Menkes steely hair syndrome definition of menkes steely. Apparently people with this disease usually have sparse, coarse, kinky hair that breaks easily. The history of john hans menkes and kinky hair syndrome. Fibroblastic cells cultured from the skin of patients and of heterozygous females show intense metachromasia in primary culture which.
Menkes disease is a fatal neurodegenerative disorder of infancy caused by diverse muta. It nearly exclusively affects males presenting at an age of 68 weeks 2,3. Female carriers are mosaics of wildtype and mutant cells due to the random x inactivation, and they are rarely affected. Menkes kinky hair disease with visual pathway defect. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar kinky hair. The atp7a gene plays an important role in controlling copper efflux from cells 3. Menkes kinky hair disease trichopoliodystrophy, steelyhair disease is an xlinked neurodegenerative disorder that occurs predominantly in males. Menkes disease md is caused by mutations in atp7a, encoding a coppertransporting ptype atpase which exhibits copperdependent trafficking. In the 52 years since the original description of menkes kinky hair disease mkhd, advances in understanding the clinical, biochemical, and molecular aspects of this rare disorder of copper metabolism have outstripped progress in the design of effective therapies.
Dec 10, 2019 menkes disease, also known as kinky hair disease, is an xlinked neurodegenerative disease of impaired copper transport. Gnidovec straiar menkes disease md is a rare genetic neurodegenerative disorder. Neonatal diagnosis and treatment of menkes disease nejm. Duodenal mucosa obtained from two patients with menkes syndrome contained abnormally large amounts of copper. Mar 30, 2020 menkes disease is a disorder that affects copper levels in the body. 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. Menkes kinky hair syndrom is a rare, xlinked recessive multisystemic lethal disorder of copper metabolism. Primary defect in copper transport underlies mottled mutants in the mouse. Survivorship was much longer than in menkes disease. Menkes disease nord national organization for rare disorders.
The characteristics facies, fair complexion, chubby cheeks, sparse twisted fuzzy depigmented hair are all present in our case. The protein gets caught in the cell membrane and cannot shuttle back and forth from the golgi apparatus copper absorption and use are impaired copper accumulates in the small intestine and kidneys. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar kinky hair are the main manifestations. The longterm findings differ completely from those initially observed and consist of undertubulation and metaphyseal flaring, similar to the findings.
Could copper deficiency be the cause of kinky hair. Menkes disease md is a rare infantile onset neurodegenerative disorder due to mutations in the x linked atp7a gene. Aka kinky hair syndrome, it is the impaired ability to metabolize copper. Learn the symptoms and treatments of menkes disease.
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