HPS consists of tyrosinase-positive albinism, a platelet storage pool defect, and lysosomal accumulation of ceroid lipofuscin, which can result in pulmonary fibrosis or granulomatous colitis. HPS occurs worldwide but primarily in NW Puerto Rico (PR). The common PR mutation is a 16 bp duplication in the HPS gene on 10q23, which produces a 79.3 kD protein of unknown function.

We studied 26 PR and 19 non-PR HPS patients 3-53 years of age. PR patients(n=23) had lower creatinine clearances compared with 19 non-PR patients, i.e., 88 ± 17 vs 107 ± 23 ml/min/1.73 sq m (p<0.005). On pulmonary function testing of 16 PR adults (mean=34y) and 7 non-PR adults (mean=32y), the PR patients had lower forced vital capacity (82 ± 20% of predicted vs 105 ± 12%, 2p<0.005) and lower carbon monoxide diffusion capacity(84 ± 25% vs 111 ± 19%, 2p<0.05). For all 44 PR and non-PR patients (mean=22y), mean total cholesterol was 181 ± 39 mg/dl (nl 50th centile, 165); LDL cholesterol was 117 ± 32 mg/dl (nl 50th centile, 110). Visual acuity ranged from 20/50 to 5/100; all showed transillumination. 5 had colitis. In biochemical studies, dolichols (lipophilic products of the cholesterol synthetic pathway) were identified in 2 HPS tissues. On lipid extraction, sloughed urinary epithelial cells displayed a thin-layer chromatography spot migrating with dolichols. Mass spectrometry (by Dr. Henry Fales, NHLBI) identified C85 dolichol in this spot. HPLC analysis measured 4-48 mcgs of dolichols/day in urinary cells from 9 HPS patients, and no dolichols in samples from 3 cystinosis patients. Autopsy lung tissue from an HPS patient (courtesy of Dr. James Loyd, Vanderbilt) exhibited 6-8 times the dolichol found in cystinosis lung. We conclude that PR and non-PR HPS differ clinically, and that dolichols constitute a significant component of ceroid lipofuscin.