Review

Authors: Zeynep Tümer, Lisbeth B Møller

Menkes disease (MD) is a lethal multisystemic disorder of copper metabolism. Progressive neurodegeneration and connective tissue disturbances, together with the peculiar 'kinky' hair are the main manifestations. MD is inherited as an X-linked recessive trait, and as expected the vast majority of patients are males. MD occurs due to mutations in the ATP7A gene and the vast majority of ATP7A mutations are intragenic mutations or partial gene deletions. ATP7A is an energy dependent transmembrane protein, which is involved in the delivery of copper to the secreted copper enzymes and in the export of surplus copper from cells. Severely affected MD patients die usually before the third year of life. A cure for the disease does not exist, but very early copper-histidine treatment may correct some of the neurological symptoms.

Topics: Adenosine Triphosphatases; Animals; Cation Transport Proteins; Copper; Copper-Transporting ATPases; Disease Models, Animal; Humans; Menkes Kinky Hair Syndrome; Mutation; Phenotype

PubMed: 19888294
DOI: 10.1038/ejhg.2009.187

Authors: Liam M Guthrie, Shivatheja Soma, Sai Yuan...

Loss-of-function mutations in the copper (Cu) transporter ATP7A cause Menkes disease. Menkes is an infantile, fatal, hereditary copper-deficiency disorder that is characterized by progressive neurological injury culminating in death, typically by 3 years of age. Severe copper deficiency leads to multiple pathologies, including impaired energy generation caused by cytochrome c oxidase dysfunction in the mitochondria. Here we report that the small molecule elesclomol escorted copper to the mitochondria and increased cytochrome c oxidase levels in the brain. Through this mechanism, elesclomol prevented detrimental neurodegenerative changes and improved the survival of the mottled-brindled mouse-a murine model of severe Menkes disease. Thus, elesclomol holds promise for the treatment of Menkes and associated disorders of hereditary copper deficiency.

Topics: Animals; Biological Transport; Brain; Cell Line; Copper; Copper Transporter 1; Disease Models, Animal; Electron Transport Complex IV; Hydrazines; Male; Menkes Kinky Hair Syndrome; Mice; Mice, Knockout; Mitochondria; Neurodegenerative Diseases; Rats

PubMed: 32381719
DOI: 10.1126/science.aaz8899

Authors: Mahmoud Reza Ashrafi, Dorsa Ghasemi, Moeinadin Safavi...

Topics: Copper; Humans; Menkes Kinky Hair Syndrome

PubMed: 35014241
DOI: 10.34172/aim.2021.138

Authors: Rozil Gandhi, Ritu Kakkar, Sajeev Rajan...

Menkes kinky hair disease is a rare X-linked recessive disease nearly exclusively affecting males who present at 2-3 months of age due to abnormal functioning of copper-dependent enzymes due to deficiency of copper. Here, we describe a completely worked-up case of a 4-month-old male infant with very typical history and radiological features confirmed by biochemical and trichoanalysis. The initially seen asymmetric cortical and subcortical T2 hyperintensities in cerebral and cerebellar hemispheres converted into symmetrical diffuse cerebral and predominantly cerebellar atrophy with uniform loss of both white and grey matter on follow-up MRI. Also, subdural hemorrhages of various sizes and different stages and tortuosity of larger proximal intracranial vessels with distal narrowing were identified. Ours is a completely worked-up proven case of Menkes kinky hair disease (MKHD) with history, electroencephalography, biochemical, trichoanalysis, and MRI findings. This is a good teaching case and shows importance of clinical examination and biochemistry as complimentary to MRI. Tortuous intracranial arteries with blocked major vessels are found only in this disease, thus stressing the value of MR Angiography in these patients.

PubMed: 22919529
DOI: 10.1155/2012/684309

Authors: Volker Rudolph, Tanja K Rudolph, Bruce A Freeman...

Topics: Adenosine Triphosphatases; Cardiovascular Diseases; Cation Transport Proteins; Copper; Copper-Transporting ATPases; Humans; Hypertension; Menkes Kinky Hair Syndrome; Mutation; Nitric Oxide; Oxidative Stress; Superoxide Dismutase

PubMed: 18768396
DOI: 10.1161/HYPERTENSIONAHA.108.117770

Authors: Anoop Verma, Kavita Menghani

Topics: Cerebral Veins; Humans; Infant; Male; Menkes Kinky Hair Syndrome

PubMed: 26840692
DOI: No ID Found

Authors: Sangita Ghosh, Soumik Chaudhuri

Menkes kinky hair syndrome, also known as trichopoliodystrophy, is a rare X-linked recessive, progressive neurodegenerative disorder characterized clinically by progressive psychomotor impairment, treatment-refractory seizures, and hair shaft abnormalities, most commonly pilli torti. The condition is related to a mutation in a copper transporting gene, located in the X-chromosome, resulting in deficiency of copper dependent enzymes. The diagnosis can be confirmed by a low plasma level of copper and ceruloplasmin. The prognosis of classical Menkes disease is poor. We report a case of Menkes kinky hair disease with characteristic clinical, laboratory, and radiological findings with significant macrocephaly (above 95th percentile for age). Reporting of this case is of significance because of its rarity and association with significant macrocephaly.

Topics: Humans; Infant; Male; Menkes Kinky Hair Syndrome

PubMed: 23217945
DOI: No ID Found

Review

Authors: A Bankier

Topics: Female; Humans; Menkes Kinky Hair Syndrome; Pregnancy

PubMed: 7783172
DOI: 10.1136/jmg.32.3.213

Authors: C S Houston, S R Harding

Topics: Humans; Infant; Male; Menkes Kinky Hair Syndrome

PubMed: 8517376
DOI: No ID Found

Review

Authors: Rahul Ojha, Asuri N Prasad

Disorders of copper homeostasis are currently recognized across the life span. Their recognition and links to human disease have spanned several decades, beginning with the recognition of a degenerative disorder in the offspring of sheep grazing in copper-deficient pastures, through to the description of infants suffering from a progressive neurodegenerative disorder characterized by epileptic seizures, developmental regression, failure to thrive, and an unusual hair quality (giving the condition its distinctive label of "kinky hair disease"). In this review, we trace the historical background and describe the biochemistry and physiology of copper metabolism and transport, inheritance patterns, molecular genetics, and genotype-phenotype correlations based on current understanding of the disorder. It is clear from the clinical presentations and variants that disorders of copper homeostasis include phenotypes ranging from mild occipital horn syndrome to intermediate and severe forms of classical Menkes disease. The symptoms involve multiple organ systems such as brain, lung, gastrointestinal tract, urinary tract, connective tissue, and skin. A multisystem disorder needs a multidisciplinary approach to care, as treatment interventions permit longer survival for some individuals. Animal models have been developed to help screen treatment options and provide a better understanding of these disorders in the laboratory. Finally, we propose a multidisciplinary approach to promote continued research (both basic and clinical) to improve survival, quality of life, and care for these conditions.

PubMed: 27574440
DOI: 10.2147/JMDH.S93454