HERMANSKY-PUDLAK SYNDROME IN A SWISS POPULATION

Tyrosinase-positive albinism, previously diagnosed as Hermansky-Pudlak Syndrome (HPS), has been examined in four generations from a village of the canton Valais, Switzerland. Homozygotes, obligate heterozygotes and putative heterozygotes in this geneology yielded lower than norma l membrane-associated thioredoxin reductase (TR) activities compared w ith normal family members and controls. All of the homozygotes and 50% of each the obligate and putative heterozygotes showed an increase in bleeding time associated with storage-pool-deficient platelets lackin g dense bodies. The TR activity profile and the platelet-dense body de ficiency in the Swiss albinos was the same as that in the HPS populati on from Puerto Rico. However, in albinos from Puerto Rico, there is an accumulation of ceroid/lipofuscin-like pigment in lysosomal structure s causing tissue damage, and, upon kidney involvement, this leads to i ncreased urinary dolichol excretion. Approximately half of the Puerto Rican HPS cases had clinical evidence of storage disease with restrict ive lung disease, granulomatous colitis, kidney failure and cardiomyop athy. By comparison, the Swiss HPS geneology had a normal life expecta ncy with no significant evidence for ceroid accumulation or urinary do lichol excretion. An examination of antioxidant enzymes, catalase, TR and glutathione reductase in epidermal suction blisters from Swiss HPS homozygotes showed a similar result for catalase and TR levels to the depigmented epidermis of patients with vitiligo, except that intracel lular TR was found to be calcium free in HPS compared with vitiligo. I ntracellular glutathione reductase levels were highest in HPS. Both th e Swiss and Puerto Rican HPS homozygotes and heterozygotes have giant melanosomes in skin melanocytes.