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Menkes disease

Tuesday 5 August 2008

Definition: Menkes disease is a X-linked recessive disease of copper transportc aused by mutation in the gene encoding Cu(2+)-transporting ATPase, alpha polypeptide (ATP7A) (MIM.300011).


- Classic severe form shows onset at 2 to 3 months of age
- Early death (usually be 3 years of age)
- A milder form has also been reported
- Incidence ranges from 1 in 40,000 to 1 in 350,000 births


- short stature
- intrauterine growth retardation (IUGR)
- microcephaly
- brachycephaly
- wormian bones
- pudgy cheeks
- intracranial hemorrhage
- osteoporosis
- joint laxity
- metaphyseal widening with spurs
- hypopigmentation
- skin laxity
- steely, kinky, sparse hair
- twisted and partial breaks on magnification
- hypertonia
- mental retardation
- seizures
- intracranial hemorrhage
- hypothermia


- Low copper
- Low ceruloplasmin


Menkes disease is caused by mutation in the gene encoding Cu(2+)-transporting ATPase, alpha polypeptide (ATP7A) (MIM.300011).

NB: The occipital horn syndrome (MIM.304150) is caused by mutation in the same gene (ATP7A).


- Christodoulou J., Danks D, et al. Early treatment of Menkès disease with parenteral cooper-histidine : long-term follow-up of four treated patients. Am J Med Genet 1998; 76 :154-64.

- Gu YH, Kodama H, Sato E, Mochizuki D, Yanagawa Y, Takayanagi M, Sato K, Ogawa A, Ushijima H, Lee CC. Prenatal diagnosis of Menkes disease by genetic analysis and copper measurement. Brain Dev. 2002;24:715-8.

- Kodama H., et al. Molecular genetics and pathophysiology of Menkès disease. Pediatr Int 1999; 41 (4) 430-5.

- Kodana H., et al. Clinical manifestation and treatment of Menkès disease and its variants. Pediatr Int 1999; 41 (4) : 423-9.

- Kodama H, Gu YH, Mizunuma M. Drug targets in Menkes disease - prospective developments. Expert Opin Ther Targets. 2001;5:625-635.

- Tumer Z., Horn N. Menkes disease : recent advances and new aspects. J Med Genet 1997; 34: 265-74.

- Tumer Z., Horn N. et al. Early copper-histidine treatment for Menkès disease (letter) Nature Genet 1996; 12 : 11-3.