Disease relevance of Menkes Kinky Hair Syndrome

• The CCC2 gene of the yeast Saccharomyces cerevisiae is homologous to the human genes defective in Wilson disease and Menkes disease [1].
• There are two major syndromes, one characterized by muscle involvement (fatal infantile or benign infantile myopathy), the other dominated by brain disease (Leigh syndrome, myoclonic epilepsy with ragged red fibers, Menkes' disease) [2].
• This is a review of case reports providing photographically documented evidence that the lines of Blaschko become manifest in the heterozygous state of various X-linked gene defects such as incontinentia pigmenti, focal dermal hypoplasia, X-linked dominant chondrodysplasia punctata, X-linked hypohidrotic ectodermal dysplasia, and Menkes syndrome [3].
• Copper is an essential nutrient that plays a fundamental role in the biochemistry of the central nervous system, as evidenced by patients with Menkes disease, a fatal neurodegenerative disorder of childhood resulting from the loss-of-function of a copper-transporting P-type adenosine triphosphatase (ATPase) [4].
• The study design was an open observational study of three children with Menkes disease and significant osteoporosis with or without pathological fractures, all of whom received pamidronate treatment for 1 year [5].

Psychiatry related information on Menkes Kinky Hair Syndrome

• Patients included seventeen with Leigh syndrome, two with Kearns-Sayre syndrome (KSS), one with myoclonus, epilepsy, and ragged red fibers (MERRF), one with Alpers disease, five with Menkes disease, two with fatty acid metabolic defect, two with Rett syndrome, and eight with unspecified mitochondrial disorders [6].

High impact information on Menkes Kinky Hair Syndrome

• Early copper-histidine treatment for Menkes disease [7].
• Menkes disease mutations and response to early copper histidine treatment [8].
• 3. On yeast artificial chromosomes from this region we have identified a sequence, similar to that coding for the proposed copper binding regions of the putative ATPase gene (MNK) defective in Menkes disease [9].
• Letter: Parenteral copper in Menkes' kinky-hair syndrome [10].
• The predicted protein encoded by the RAN1 gene is similar to the Wilson and Menkes disease proteins and yeast Ccc2 protein, which are integral membrane cation-transporting P-type ATPases involved in copper trafficking [11].

Chemical compound and disease context of Menkes Kinky Hair Syndrome

• Direct involvement of the N-terminal domains in the binding of copper suggests their important role in copper-dependent functions of human copper-transporting adenosine triphosphatases (Wilson's and Menkes disease proteins) [12].
• Kinetics of Cu(II) transport and accumulation by hepatocytes from copper-deficient mice and the brindled mouse model of Menkes disease [13].
• The urinary deoxypyridinoline level was significantly low in the patients with Menkes' disease, indicating that it is a good marker of lysyl oxidase activity, which is related to the connective tissue abnormalities [14].
• Its hemizygote, which is considered to be a model of Menkes kinky hair disease (MKHD), was injected intraperitoneally four times with 10, 20, 20 and 30 micrograms of cupric chloride on days 4, 6, 8 and 10, respectively [15].
• A male infant with Menkes Kinky Hair Syndrome was treated with a 3-week course of cupric acetate infusions, which was terminated when he developed aminoaciduria [16].

Biological context of Menkes Kinky Hair Syndrome

• Recently, it was reported that ATP7A-transcript levels as low as 2%-5% of normal are sufficient to result in the milder phenotype, OHS, rather than the phenotype of Menkes disease [17].
• A novel frameshift mutation in exon 23 of ATP7A (MNK) results in occipital horn syndrome and not in Menkes disease [17].
• 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 [18].
• Novel membrane traffic steps regulate the exocytosis of the Menkes disease ATPase [19].
• To correlate genotype with response to early copper histidine therapy in Menkes disease, an X-linked disorder of copper transport, we performed mutational analysis in 2 related males who began treatment at the age of 10 days and prenatally at 32 weeks' gestation, respectively [20].

Anatomical context of Menkes Kinky Hair Syndrome

• Fibroblast cultures from 12 unrelated patients with classical Menkes disease were analyzed for mutations in the MNK gene, by reverse transcription-PCR (RT-PCR) and chemical cleavage mismatch detection [21].
• The Menkes disease gene encodes a P-type transmembrane ATPase (ATP7A) that translocates cytosolic copper ions across intracellular membranes of compartments along the secretory pathway [22].
• In this study, a Menkes disease mutation, G1019D, located in the large cytoplasmic loop of MNK, was characterized in transfected cultured cells [23].
• The delineation of a distinctive neurochemical pattern in plasma and cerebrospinal fluid, reflecting deficiency of the copper enzyme dopamine beta-monooxygenase, is arguably the most important finding in the study of Menkes syndrome [24].
• It is suggested that the decrease in lysyl oxidase activity would help to explain the connective tissue defects observed in Menkes' syndrome, and that this reduction, in conjunction with the elevated concentrations of cellular copper, would support the hypothesis that a functional intracellular copper deficiency exists in Menkes' syndrome [25].

Gene context of Menkes Kinky Hair Syndrome

• The gene ATP7B responsible for Wilson's disease (WD) produces a protein which is predicted to be a copper-binding P-type ATPase, homologous to the Menkes disease gene (ATP7A) [26].
• Menkes disease is a fatal disease that can be induced by various mutations in the ATP7A gene, leading to unpaired uptake of dietary copper [27].
• This process, which requires both Gef1 and the Menkes disease Cu2+-ATPase yeast homolog Ccc2, occurs in late- or post-Golgi vesicles, where Gef1 and Ccc2 are localized [28].
• Characterization of the interaction between the Wilson and Menkes disease proteins and the cytoplasmic copper chaperone, HAH1p [29].
• An animal model of kinky hair syndrome is provided by mice mutant at the X-linked mottled locus [30].

Analytical, diagnostic and therapeutic context of Menkes Kinky Hair Syndrome

• In the present study, we report the use of three fast and reliable polymerase chain reaction (PCR)-based methods for the identification of partial ATP7A deletions in Menkes disease patients [31].
• Intraperitoneal injections of cupric chloride prevent neuronal degeneration in the hemizygous brindled mottle mouse, MO br/Y, a murine model of kinky hair syndrome (KHS) in humans [32].
• Carrier detection for 12 women and prenatal diagnosis for six fetuses in Japanese families with a patient with Menkes disease (MNK) were performed by gene analysis and/or measurement of the copper concentration in cultured cells [33].

References