Genetically transmitted metabolic disorder causing albinism, visual impairment, platelet pool storage deficiency resulting in bleeding diathesis, and lysosomal accumulation of ceroid lipofuscin resulting in pulmonary fibrosis, inflammatory bowel disease, and renal insufficiency.
N.B.: “Hermansky” is often misspelled as “Hermanski.”
Albinism with Hemorrhagic Diathesis; Oculocutaneous Albinism type VIA; Platelet Delta Storage Pool Disease; Albinism Hemorrhagic Diathesis Syndrome; Albinism-Thrombocytopathy Syndrome; Oculocutaneous Albinism-Hemorrhagic Diathesis Syndrome.
Inherited disorder of metabolism of ceroid lipofuscin first reported in 1959 by the Czech internist Frantisek Hermansky and P. Pudlak. They described two patients with oculocutaneous albinism and bleeding diathesis.
The third most common type of albinism affecting diverse ethnic populations, mainly in Puerto Rico and the Swiss Alps. The highest incidence is observed in the Puerto Rican general population, with a prevalence of at least 1:1,800. In Puerto Rico, approximately 1:21 persons carry the gene encoding HPS. Also, five of six Puerto Ricans with oculocutaneous albinism have HPS. However, the disease is by no means restricted to this population, and clusters exist in most populations internationally. It is considered to affect around 1 in 500,000 people worldwide.
This autosomal recessive disorder is caused by a mutation within the gene HPS1 which is consisting of a 16-bp duplication and localized on chromosome 10q23. It encodes a transmembrane protein locus that is likely to be a component of multiple cytoplasmic organelles, the granular fraction of melanocytes, and the cytoplasm of nonmelanotic cells.
In addition to the photophobia and hypopigmentation of eyes, skin, and hair exhibited by other albinos, patients with HPS demonstrate a mild bleeding diathesis. This is a result of a combination of impaired platelet function caused by storage pool deficiency and of accumulation of ceroid in tissues. As well as impairing coagulation, ceroid accumulation results in fibrosis in various sites, resulting in organ damage.
The combination of albinism with ceroid deposition and bleeding diathesis defines HPS. For proper diagnosis the platelets must be examined by electron microscopy, which reveals the absence of dense bodies.
Wide variety of phenotypic appearances. Bleeding disorders and ocular anomalies, including blindness, nystagmus, iris transillumination, foveal hypoplasia, and albinotic retinal midperiphery, are often revealing symptoms. Albinism is tyrosinase positive, which means that patients present with varied amounts of pigmentation. A light skin color associated with numerous freckles, hypertrichosis of the eyelashes, and trichomegaly on the arms and legs are found in 36% of affected individuals. Acanthosis nigricans like lesions (without pigmentation) are found in 29% of HPS1-positive patients. Bruising is normally observed in more than 90% of patients. In later childhood and subsequently during the adult life, the fibrosis is caused by ceroid ...