Menkes Syndrome

Introduction: Menkes Syndrome, also know as Kinky Hair Disease, is a recessively inherited X chromosomal gene which disrupts copper metabolism and decreases a cells' ability to absorb copper. Research suggests that this disease is caused by

a mutation in the gene encoding Cu(2+)-transporting ATPase, alpha polypeptide

(OMIM #309400). First described in 1962, Menkes causes cerebral degeneration, seizures, hair that appears both kinked and lightly pigmented under the microscope, and will often result in death within the first year of life. This disease affects 1 in every 50,000-250,000 births with the average life expectancy of a patient with this disease is between 6 months and 3 years (eMedicine). (General Summary of Disease; History of Disease)


Gene Information: According to eMedicine,

the Menkes gene is located on the long arm of the X chromosome at Xq13.3 (ATP7A), and the gene product is a 1500-amino-acid P type adenosine triphosphatase (ATPase), which has 17 domains -- 6 copper binding, 8 transmembrane, a phosphatase, a phosphorylation, and an ATP binding.

In normal nondiseased cells, this ATPase transports copper into the secretory pathway of the cell for incorporation and excretion. When cells are affected by Menkes Disease, import of dietary copper is impared leading to unhealthy accumulation of copper in various organs like the kidneys while other organs such as the brain have an unhealthy lack of copper. Mutations of this gene are also know to cause Occipital horn syndrome, another copper transport disease that causes wedge-shaped calcifications on the skull. (Nucleotide Information; Entrez Gene)


Homologs:
Homologene- Notes the similarities between the gene, proteins, and pheontypes of Menkes Syndrome in H. sapiens and other organisms.
Unigene- Shows information on gene expression and mRNA and EST sequences as well as protein sequence similarities between humans and other organisms including E. coli, M. musculus, and C. elegans.


Symptoms: Symptoms include loss of developmental milestones, hypotonia, cerebral degeneration, seizures, temperature instability, hair that appears both kinked and lightly pigmented under the microscope, abnormal facial features such as depressed nasal bridge or sagging cheeks, and skin laxity. Once the symptoms are observed, microscopical examining the hair or testing copper levels are the most common methods for confirming the disease. In some cases genetic tests are done to prove mutations in the ATP7A gene.

Treatment: Oral, subcutaneous, and intravenous supplements of copper have shown to help symptoms but not the progression of the disease. Alternative therapies are still being investigated. Parents can undergo genetic screenings to identify possible carriers and evaluate potential pregnancy risks.

Additional Links:
The Medical Directory- Contains useful diagrams illustrating and explaing patterns of inheritance of Menkes
Pubmed- Scholarly articles about Menkes Syndrome
Genetics Home Reference- The U.S. National Library of Medicine's simple reference page on the genetic condition- contains many additional links about research institutions, articles of interest, clinical trials, patient support, etc.
NINDS- General summary of Menkes Syndrome by the The National Institute of Neurological Disorders and Stroke which supports and funds research on this disease. Can link to organizations looking for Menkes patients for various studies.