Clinical manifestations and treatment of Menkes disease and its variants

Abstract

The clinical manifestations of classical Menkes disease, mild Menkes disease and occipital horn syndrome are reviewed. Menkes disease is a neurodegenerative disease with X-linked recessive inheritance. Orally administered copper accumulates in the intestine, resulting in the failure of copper absorption. The primary metabolic defect that causes copper accumulation in the intestine is present in almost all extrahepatic tissues. The blood, liver and brain are in a state of copper deficiency, which is due to defective copper absorption. The characteristic features, including neurological disturbances, arterial degeneration and hair abnormalities, can be explained by the decrease in cuproenzyme activities. DNA-based diagnosis is now possible. Mild Menkes disease and occipital horn syndrome, which show milder forms than Menkes disease, have been identified as genetic disorders resulting from mutations in the Menkes disease gene. Because the clinical spectrum of Menkes disease is wide, males with mental retardation and connective tissue abnormalities should be evaluated for biochemical evidence of defective copper transport. The treatment accepted currently is parenteral administration of copper. When treatment is started in patients with classical Menkes disease above the age of 2 months, it does not improve the neurological degeneration. When the treatment is initiated in newborn babies affected with this disease, the neurological degeneration can be prevented in some, but not all, cases. Moreover, early treatment cannot improve non-neurological problems, such as connective tissue laxity. Therefore, alternative therapies for Menkes disease and occipital horn syndrome should be studied.

Menkes disease: A case report

“…The classical form of MD comprises a neurological degenerative syndrome (cognitive compromise, ataxia, seizures, retarded neurological development), arterial abnormalities, bony changes like osteoporosis, bladder diverticulum , changes of connective tissue and skin and hair abnormalities (pili torti, monilethrix and trichorrhexis nodosa) [1][2][3][4][5] . Over time neurological symptoms and arterial anomalies of abdominal and cranial arteries become more severe, with symptoms suggestive of symptomatic West's syndrome, or conversely a drug-resistant progressive epileptic syndrome 5,11,12 .…”

“…Menkes' disease (MD) is a degenerative disease, with an X-linked recessive inheritance, characterized by involvement of the nervous system due to an intracellular defect of the copper transport protein [1][2][3][4][5] . Clinical diagnosis can be confirmed by quantifying serum and urinary levels of copper, serum ceruloplasmin level and genetic study 5 .…”

“…Clinical diagnosis can be confirmed by quantifying serum and urinary levels of copper, serum ceruloplasmin level and genetic study 5 . Nevertheless, neurophysiological studies and muscle biopsy can be used to helping in the diagnosis 6 .…”

Menkes' disease: case report

“…The treatment options are limited because the brain-blood barrier acts as an obstacle to copper delivery without the transporter protein 1,2,5,16,17 . Also, copper is poorly absorbed by the gastrointestinal tract, without attaining an adequate serum level, mainly as copper histidine by parenteral reposition (200-1000 µg/day), might be beneficial in some cases when given early in the course of the disease 2,5,16,17 .…”

“…Also, copper is poorly absorbed by the gastrointestinal tract, without attaining an adequate serum level, mainly as copper histidine by parenteral reposition (200-1000 µg/day), might be beneficial in some cases when given early in the course of the disease 2,5,16,17 . There is no evidence, at present, of benefit of parenteral administration of copper associated with Dpenicillamine or vitamin E 5 .…”