Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder in which oculocutaneous albinism, bleeding, and lysosomal ceroid storage result from defects of multiple cytoplasmic organelles: melanosomes, platelet-dense granules, and lysosomes.
Synopsis
ocular anomalies
epistaxis
gingival bleeding
cardiomyopathy
interstitial pulmonary fibrosis (restrictive lung disease)
granulomatous colitis (inflammatory bowel disease)
renal failure
cutaneous anomalies
coagulation anomalies
pigmented reticuloendothelial cells
Etiology
Hermansky-Pudlak syndrome is a disorder of abnormal biogenesis of lysosomes and related organelles. Six genes are now identified causing HPS in humans (HPS-1 to HPS-6). Some HPS-gene products are part of distinct protein complexes: the adaptor complex AP-3, and six different BLOCs (Biogenesis of Lysosome-related Organelles Complex).
HPS1 (MIM.604982) at 10q23.1
HPS2: AP3B1 (MIM.603401) at Chr.5
HPS3 (MIM.606118) at 3q24
HPS4 (MIM.606682) at Chr.22
HPS5 (MIM.607521) at 11p15-p13
HPS6 (MIM.607522) at 10q24.32
HPS7: DTNBP1 (MIM.607145) at 6p22.3
HPS to extensively characterize each subtype. Clinically, all patients show oculocutaneous albinism and storage pool deficiency. HPS-1 and HPS-4 also exhibit occasional granulomatous colitis and fatal pulmonary fibrosis. HPS-2 patients show persistent neutropenia and childhood infections. HPS-3, and perhaps HPS-5 and HPS-6 patients have a milder form of the disease with occasional granulomatous colitis.
References
Anderson PD, Huizing M, Claassen DA, White J, Gahl WA. Hermansky-Pudlak syndrome type 4 (HPS-4): clinical and molecular characteristics. Hum Genet. 2003 Jul;113(1):10-7. Epub 2003 Mar 27. PMID: #12664304#
Griffiths GM. Albinism and immunity: what's the link? Curr Mol Med. 2002 Aug;2(5):479-83. PMID: #12125813#
Huizing M, Gahl WA. Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. Curr Mol Med. 2002 Aug;2(5):451-67. PMID: #12125811#