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).
Epidemiology
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
Synopsis
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
LABORATORY
Low copper
Low ceruloplasmin
Etiology
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).
References
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.