Hermansky-Pudlak syndrome type 4 with interstitial pneumonia

Abstract

Hermansky-Pudlak syndrome (HPS) is an autosomal recessive disorder characterized by oculocutaneous albinism, bleeding tendency, and lysosomal accumulation of ceroid-like material, with occasional development of interstitial pneumonia (IP). Nine genetically distinct subtypes of HPS are known in humans; IP develops primarily in types 1 and 4. Most reported cases of HPS with IP are type 1, and there are no published reports of type 4 in Japanese individuals. A 58-year-old man with congenital oculocutaneous albinism and progressive dyspnea for 1 month was admitted to our hospital. We administered high-dose corticosteroids on the basis of a diagnosis of acute exacerbation of interstitial pneumonia. Respiratory symptoms and the findings of high-resolution computed tomography (CT) showed improvement. He was diagnosed with HPS type 4 with interstitial pneumonia on the basis of gene analysis. He has been receiving pirfenidone for 1 year and his condition is stable. This is the first report on the use of pirfenidone for HPS with IP caused by a novel mutation in the HPS4 gene. We conclude that HPS should be suspected in patients with albinism and interstitial pneumonia. High-dose corticosteroid treatment may be useful in cases of acute exacerbation of interstitial pneumonia due to HPS-4, and pirfenidone may be useful and well tolerated in patients with HPS-4.

Keywords: Corticosteroid; Hermansky–Pudlak syndrome; Oculocutaneous albinism; Pirfenidone; Pulmonary fibrosis.

Fig. 1

Patient's appearance. Left, note the blond hair and albinism. Right, the blond body hair and erythema at sites of exposure to sunlight.

Fig. 2

Chest radiograph showing bilateral volume loss and lower lobes with dominantly diffuse linear and reticular opacity, with ground-glass opacity in both lung fields.

Fig. 3

A–B, CT scan of right lung at time of admission. C–D, same slices of right lung 2 months later, showing improvement of ground-glass opacity and reticulonodular pattern as the result of treatment. E–F, same slices of right lung at 1 year after admission, showing gradual progression of disease.

Fig. 4

Bone marrow biopsy showing macrophages containing ceroid-like materials.

Fig. 5

Sequence analysis of exon 13 in HPS4 gene using genomic DNA samples from the patient and his mother reveals the novel mutation, c.1858C > T (p.Q620X), homozygously in the patient and heterozygously in his mother. The mutation was also detected in his sister and his daughter (data not shown).