Elevated urinary dolichol excretion in the Hermansky-Pudlak syndrome. Indicator of lysosomal dysfunction.

The Hermansky-Pudlak syndrome, a triad of albinism, platelets lacking dense bodies, and storage of ceroid-like material in tissues, occurs approximately once in 2,000 northwestern Puerto Ricans. The manifestations of storage disease are variable and include granulomatous colitis, restrictive lung disease, kidney failure, and cardiomyopathy. The autofluorescent material stored in the Hermansky-Pudlak syndrome is histochemically similar to that stored in neuronal ceroid/lipofuscinosis. The material in neuronal ceroid/lipofuscinosis contains dolichols, which are components of lysosomes, and patients show increased urinary excretion of dolichols. This study of 49 patients with the Hermansky-Pudlak syndrome found that urinary dolichol levels are increased in those patients with evidence of ceroid storage in the kidneys but are not elevated when storage occurs in tissues other than the kidneys. The excretion of ceroid was not influenced by the saturation state of dietary fat. A defect in processing of membranes of lysosomes, melanosomes, and dense bodies may be involved in the syndrome.

Oxidation of dopa in human albinism.

The urine of an albino woman contained small quantities of 5-S-cysteinyldopa; 6-hydroxy-5-methoxyindole-2-carboxylic acid, a melanin precursor metabolite, was lacking. The 5-S-cysteinyldopa excretion observed may reflect non-specific oxidation of dopa. Two other albino patients showed normal values for the excretion of 5-S-cysteinyldopa and of 6-hydroxy-5-methoxyindole-2-carboxylic acid.

Urinary excretion of 5-S-cysteinyldopa and 6-hydroxy-5-methoxyindole-2-carboxylic acid: differences between pigmented and albino mice.

Urinary excretion of the phaeomelanin precursor 5-S-cysteinyldopa (5-S-CD) and the eumelanin metabolite 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI-2-C) was studied in black and albino mice. The urinary concentration of 5-S-CD was 31.7 ng/ml in black and 16.1 ng/ml in albino mice. The concentration of 6H5MI-2-C was 21.0 ng/ml in the urine of black mice. The compound could not be demonstrated in the urine of albino mice.

Copper metabolism study in oculocutaneous albinism.

Abnormal copper metabolism has been described in some pigmentary retinopathies. Albinism is a manifestation of a metabolic disorder in which lack of pigmentation is a prominent feature and changes in the retinal pigment epithelium are found as well. We examined the blood and urine of two groups of patients, albino and control groups, for copper, zinc and ceruloplasmin in serum and copper excretion in urine. We found in the albino group, elevated values of ceruloplasmin which was highly significant when compared to the control group. The mean copper concentration in serum was found to be high as well. The urinary copper was distinctly elevated in four patients of the albino group. Therefore, our results suggest that there might be a primary abnormality of copper metabolism in these patients.