GENETIC-DEFECTS AND CLINICAL CHARACTERISTICS OF PATIENTS WITH A FORM OF OCULOCUTANEOUS ALBINISM (HERMANSKY-PUDLAK SYNDROME)

Background Hermansky-Pudlak syndrome is characterized by oculocutaneou s albinism, a storage-pool deficiency, and lysosomal accumulation of c eroid lipofuscin, which causes pulmonary fibrosis and granulomatous co litis in some cases. All identified affected patients in northwest Pue rto Rico are homozygous for a 16-bp duplication in exon 15 of a recent ly cloned gene, HPS. We compared the clinical and laboratory character istics of these patients with those of patients without the 16-bp dupl ication. Methods Forty-nine patients - 27 Puerto Ricans and 22 patient s from the mainland United States who were not of Puerto Rican descent - were given a diagnosis on the basis of albinism and the absence of platelet dense bodies. We used the polymerase chain reaction to determ ine which patients carried the 16-bp duplication. Results Twenty-five of the Puerto Rican patients were homozygous for the 16-bp duplication , whereas none of the non-Puerto Rican patients carried this mutation. Like the patients without the duplication, the patients with the 16-b p duplication had a broad variation in pigmentation. Nine of 16 adults with the duplication, but none of the 10 without it, had a diffusing capacity for carbon monoxide that was less than 80 percent of the pred icted value. High-resolution computed tomography in 12 patients with t he 16-bp duplication revealed minimal fibrosis in 8, moderate fibrosis in 1, severe fibrosis in 1, and no fibrosis in 2. Computed tomography in eight patients without the duplication revealed minimal fibrosis i n three and no fibrosis in the rest. Inflammatory bowel disease develo ped in eight patients (four in each group) between 3 and 25 years of a ge. Conclusions The 16-bp duplication in exon 15 of HPS, which we foun d only in Puerto Rican patients, is associated with a broad range of p igmentation and an increased risk of restrictive lung disease in adult s. (C)1998, Massachusetts Medical Society.