A 26-year-old woman was admitted to our institution for cyclic neutropenia and hepatitis B viral infection. Clinical examination revealed hair and cutaneous hypopigmentation and bilateral nystagmus. Leukocyte and neutrophil counts were 1700 and 500/μL, respectively. Platelet count was 185,000/μL. Liver tests showed minimal elevation of alanine aminotransferase and slightly prolonged prothrombin time. Serum aspartate aminotransferase, alkaline phosphatase, γ-glutamyl transpeptidase, bilirubin, immunoglobulins, and albumin were within normal ranges. The patient was positive for serum hepatitis B surface antigen, and there was no evidence for hepatitis C, hepatitis D, herpes, or cytomegalovirus infection. Percutaneous liver biopsy showed moderately active chronic hepatitis with bridging fibrosis and numerous ground-glass hepatocytes. One striking finding was the presence of small aggregates of macrophages, mainly portal, containing in their cytoplasm a granular material (Fig. A) that was stained by periodic acid-Schiff with (Fig. B) and without diastase pretreatment and by Fontana's technique (Fig. C). These granules were strongly autofluorescent under ultraviolet light, were not refringent under polarized light, and corresponded to ceroid lipofuscin (Fig. D). Such lipofuscin-type granules resemble those observed in Dubin-Johnson syndrome but, in this latter condition, they are localized in the cytoplasm of the hepatocytes, mainly around terminal hepatic veins, and not in the cytoplasm of the macrophages. The fluorescent hepatocellular inclusions noted in porphyria cutanea tarda, and corresponding to uroporphyrin accumulation, are different because they are needle-shaped and refringent under polarized light.
Accumulation of ceroid lipofuscin within macrophages in a patient with hair and cutaneous hypopigmentation, nystagmus, and cyclic neutropenia is consistent with the disease described in 1959 by Hermansky and Pudlak in two albinos with severe bleeding.1 Hermansky-Pudlak syndrome (HPS) belongs to the group of genetic diseases of lysosome-related organelle biogenesis, which also includes Chediak-Higashi and Griscelli syndromes, as well as platelet granule-specific disorders such as Wiskott-Aldrich syndrome.1 Prevalence of HPS is high in Puerto Rico, where this autosomal recessive disease affects 1 in 1800 persons.2, 3 Patients usually have hypopigmentation with abnormal melanosomes, reduced visual acuity, and may present renal dysfunction with ceroid accumulation in tubular cells. Granulomatous colitis can be observed, and major causes of death are hemorrhage and pulmonary interstitial fibrosis with intra-alveolar ceroid-laden macrophages.2, 3 Eight human HPS genes are known: they encode components of ubiquitously expressed protein complexes involved in intracellular protein trafficking and lysosome-related organelle distribution.1 Mutations of these genes result in a defect in the processing of lysosomal membranes and probably explain the microscopically visible accumulation of ceroid lipofuscin in various cellular types of the organism.1