Hermansky-Pudlak Syndrome with Interstitial Pneumonia without Mutation of HSP1 Gene

Abstract

A 57-year-old man with occulocutaneous albinism was admitted to our hospital because of exertional dyspnea and an abnormal shadow on chest roentgenogram. Chest CT revealed diffuse interstitial shadows with reticulonodular opacities in the bilateral whole lung fields and his pulmonary function test was consistent with a restrictive finding. Histologically, intraluminal diffuse fibrosis and interstitial fibrosis existed and ceroid-like materials within alveolar macrophages were demonstrated in a transbronchial lung biopsy specimen. In addition, because platelet dysfunction and ceroid-like materials within the reticuloendothelial cells of urine and bone marrow aspiration were recognized, we made a diagnosis of Hermansky-Pudlak syndrome (HPS). Gene analysis of the patient's peripheral blood cells did not reveal that he was a compound homogeneity for HPS1 gene mutations.

Hermansky-Pudlak Syndrome with Nonspecific Interstitial Pneumonia

“…HPS1 is the most common subtype and can cause severe comorbidities such as interstitial pneumonia or inflammatory bowel disease (2)(3)(4)(5)11). In addition, HPS4 patients characteristically develop severe interstitial pneumonia as well as HPS1 (2,5).…”

“…An arterial blood gas analysis showed a PaO2 of 92. 4 Torr and a PaCO2 of 30.0 Torr on room air. Her oxygen saturation level was 97% on room air at rest; however, it decreased to 87% during a 6-minute walk test.…”

“…There are eight known human HPS genes causing different subtypes of HPS (HPS1-8) (2). In particular, patients with HPS1 and HPS4 gene mutations frequently develop interstitial pneumonia, the most serious complication of HPS (3)(4)(5). The pathological features and patterns of interstitial pneumonia in patients with HPS (HPS-IP) have not been fully elucidated, and no effective treatments have been reported (6)(7)(8), except for lung transplantation (9).…”

Respiratory manifestations in patients with inherited metabolic diseases

“…Lysosomal ceroid-like lipofuscin accumulates in the reticuloendothelial system, particularly in alveolar macrophages. Among the different types, Hermansky-Pudlak syndrome-1 is the subtype most frequently associated with increased lung disease risk [61,62]. Patients with HermanskyPudlak syndrome, especially females, may develop pulmonary fibrosis with excessive inflammatory cells and lipofuscin ceroid within the alveolar macrophages [63].…”

Shared Mechanisms of Lung Injury and Subsequent Fibrosis: Role of Surfactant Proteins in the Pathogenesis of Interstitial Pneumonia in Hermansky-Pudlak Syndrome

“…HPS with interstitial pneumonia is primarily associated with HPS1 gene abnormality, located in chromosome 10q23.1-q23.3 (2). Kobashi et al reported typical features of the clinical manifestations in an HPS patient with interstitial pneumonia without mutation of HPS1 gene (3). A case with a normal HPS1 gene progressing to interstitial pneumonia associated with HPS is very intriguing.…”