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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.
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NB: “Hermansky” is often misspelled as “Hermanski.”
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Albinism with Hemorrhagic Diathesis; Oculocutaneous
Albinism type VIA; Platelet Delta Storage Pool Disease; Albinism Hemorrhagic
Diathesis; Albinism-Thrombocytopathy; Oculocutaneous Albinism-Hemorrhagic
Diathesis Syndrome.
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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.
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The third most common type of albinism affecting diverse
ethnic populations, mainly in Puerto Rico and the Swiss Alps. The highest
incidence is in the Puerto Rican general population, with a prevalence of at
least 1:1000. 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.
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This autosomal recessive disorder is caused by
a mutation within the gene HPS1 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.
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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.
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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.
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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 adult life, the
fibrosis caused by ceroid deposition causes considerable physical limitation
because of development of fibrotic restrictive lung disease. Gingivitis is complicated
by dental problems, and the resulting surgery is complicated by
bleeding. ...