Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022716 (Menkes)
 1,057 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 19-year-old female patient, who had exhibited esotropia, mild cerebellar ataxia, mild mental retardation, and cerebellar atrophy on magnetic resonance images at the age of 15, developed signs of acute encephalopathy, and thereafter died of disseminated intravascular coagulation on the day of her admission. Both her mother and sister suffered from attacks of hemiplegic migraine, mild mental retardation, and cerebellar ataxia. Neuropathological examinations revealed acute changes in the widespread cerebral cortex, chronic degenerative changes in the anterior lobe of the cerebellar vermis, axonal spheroids in the Goll's nucleus, pseudo-calcinosis in the globus pallidus, and glial bundles in the cranial nerves. The most fascinating features were changes of Purkinje cells, such as cactuses (asteroid bodies, dendritic expansions), somatic sprouts, and torpedoes. These changes may be characteristic of familial hemiplegic migraine with cerebellar atrophy, as well as the other metabolic diseases, such as Menkes' kinky hair disease, infantile (Tay-Sachs type) amaurotic idiocy, organic mercury intoxication, and mitochondrial encephalopathy, of which cases often exhibit such pathological changes of Purkinje cells. Therefore, familial hemiplegic migraine may share some metabolic abnormalities with the diseases mentioned above.
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PMID:Autopsy case of acute encephalopathy linked to familial hemiplegic migraine with cerebellar atrophy and mental retardation. 1619 40

X-linked congenital cerebellar ataxia is a heterogeneous nonprogressive neurodevelopmental disorder with onset in early childhood. We searched for a genetic cause of this condition, previously reported in a Buryat pedigree of Mongolian ancestry from southeastern Russia. Using whole-genome sequencing on Illumina HiSeq 2000 platform, we found a missense mutation in the ABCB7 (ABC-binding cassette transporter B7) gene, encoding a mitochondrial transporter, involved in heme synthesis and previously associated with sideroblastic anemia and ataxia. The mutation resulting in a substitution of a highly conserved glycine to serine in position 682 is apparently a major causative factor of the cerebellar hypoplasia/atrophy found in affected individuals of a Buryat family who had no evidence of sideroblastic anemia. Moreover, in these affected men we also found the genetic defects in two other genes closely linked to ABCB7 on chromosome X: a deletion of a genomic region harboring the second exon of copper-transporter gene (ATP7A) and a complete deletion of PGAM4 (phosphoglycerate mutase family member 4) retrogene located in the intronic region of the ATP7A gene. Despite the deletion, eliminating the first of six metal-binding domains in ATP7A, no signs for Menkes disease or occipital horn syndrome associated with ATP7A mutations were found in male carriers. The role of the PGAM4 gene has been previously implicated in human reproduction, but our data indicate that its complete loss does not disrupt male fertility. Our finding links cerebellar pathology to the genetic defect in ABCB7 and ATP7A structural variant inherited as X-linked trait, and further reveals the genetic heterogeneity of X-linked cerebellar disorders.
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PMID:Whole-genome sequencing identifies a novel ABCB7 gene mutation for X-linked congenital cerebellar ataxia in a large family of Mongolian ancestry. 2624 92

Menkes disease is an X-linked multisystem disorder with epilepsy, kinky hair, and neurodegeneration caused by mutations in the copper transporter ATP7A. Other ATP7A mutations have been linked to juvenile occipital horn syndrome and adult-onset hereditary motor neuropathy.1,2 About 5%-10% of the patients present with "atypical Menkes disease" characterized by longer survival, cerebellar ataxia, and developmental delay.2 The intracellular copper transport is regulated by 2 P type ATPase copper transporters ATP7A and ATP7B. These proteins are expressed in the trans-Golgi network that guides copper to intracellular compartments, and in copper excess, it relocates copper to the plasma membrane to pump it out from the cells.3ATP7B mutations cause Wilson disease with dystonia, ataxia, tremor, and abnormal copper accumulation in the brain, liver, and other organs.4.
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PMID:Phenotypic convergence of Menkes and Wilson disease. 2787 36