Menkes' Kinky-Hair Syndrome

Abnormal Copper Metabolism in Menke's Steely-Hair Syndrome

“…The oral loading data in patients 2 and 3 confirm our fmdings reported in patient 1 (22) and indicate that the absorption defect in SHS may be incomplete in some patients. Dekaban et al (5) have found approximately 25% residual absorption in three patients, and Danks et al (3) cited two cases which showed increases in serum Cu after Cu sulfate loading, commensurate with our findings in case 3. Walker-Smith et al (27) noted a rise in serum Cu concentration from 5 to 37 pg/ 100 ml after 6 months of oral Cu sulfate therapy.…”

“…Replenishment of Cu deficiency through parenteral supplementation has not yielded impressive clinical results. At best, there is a mild subjective improvement (2,3,6) or a partial arrest of symptomatic psychomotor deterioration (17), but a recent report fails to demonstrate even these modest gains (13). We have presented morphologic evidence (28) through Golgi impregnation of brain that a prenatal developmental anomaly exists in Purkinje cell dendrites.…”

“…Danks et al (3) found that erythrocyte Cu concentrations were normal in four SHS infants, suggesting a preferential retention of Cu by red blood cells. Elevated Cu concentrations have also been demonstrated in liver (5, 16), skin fibroblasts (4,14), amniotic fluid cells (19), and small intestine (2,3) in the disorder. Excessive urinary (1 1) and fecal (6) excretion of Cu has been reported in SHS, along with unresponsiveness of Cu metalloenzymes (12).…”

“…In 1972, Danks et al (3) demonstrated a deficiency in the intestinal absorption of Cu in SHS and suggested that a general dysfunction in Cu containing enzymes might account for the keratin and collagen abnormalities, cerebrovascular disease, scorbutic bone changes, and hypothermia commonly seen in the disorder. Although Cu deficiency, as reflected by the low levels of serum Cu and ceruloplasmin, has been found to be a universal feature of the disease, emerging evidence suggests that defective intestinal absorption of the metal may be only part of a more widespread disorder of Cu transport and/or binding.…”

Neuroimaging Changes in Menkes Disease, Part 1

“…Intracranial artery elongation has been related to decreased activity of the copper-dependent lysyl oxidase, which is involved in elastin and collagen cross-linking, resulting in structural impairment of the blood vessel wall. [9][10][11][12][13][14][15] Because during the whole intrauterine life, the circulating copper is provided by the mother, early vascular wall impairment points to a key role of ATP7A for lysyl oxidase function within the cell. 16 The absence of intracranial artery ectasia and stenosis, either at onset or at follow-up, is another important result.…”