Zhang et al. (2003) described a 39-year-old Belgian woman with Hermansky-Pudlak syndrome-6. She had oculocutaneous albinism and frequent prolonged nosebleeds, as well as prolonged bleeding after dental extractions and surgery. She had no pulmonary or gastrointestinal symptoms. Her ... Zhang et al. (2003) described a 39-year-old Belgian woman with Hermansky-Pudlak syndrome-6. She had oculocutaneous albinism and frequent prolonged nosebleeds, as well as prolonged bleeding after dental extractions and surgery. She had no pulmonary or gastrointestinal symptoms. Her platelet count was normal, and her bleeding time was moderately prolonged. Platelet function test showed reduced secretion in response to ATP. Electron microscopy of her platelets showed only very rare dense granules. Her parents had no known consanguinity, but both were from the same small region of east Flanders. A brother was similarly affected. Schreyer-Shafir et al. (2006) studied a large consanguineous Israeli Bedouin family in which the Hermansky-Pudlak syndrome phenotype was characterized mainly by oculocutaneous albinism. Electron microscopic studies of platelets showed absence of dense bodies, consistent with HPS, and confocal microscopy revealed abnormal distribution of LAMP3 (605883) in patient fibroblasts, indicating abnormal trafficking of lysosomal-related organelles. The findings expanded the phenotype associated with mutations in the HPS6 gene. Huizing et al. (2009) described 4 patients with Hermansky-Pudlak syndrome-6. The first was a 36-year-old woman of Irish and German descent who was found to have partial albinism and nystagmus at age 5 months, but diagnosis was not made until age 26 when bleeding complications were followed up, revealing an absence of platelet dense bodies. She also had multiple abdominal surgeries for hernia, imperforate anus, and gluteal flap repairs. She had other medical problems, including 4 miscarriages, endometriosis, frequent upper respiratory and urinary tract infections, incontinence, migraine headaches, and hearing loss. However, she did not have granulomatous colitis, and renal and pulmonary functions were normal. The second patient was a 22-year-old man of northern European descent who had nystagmus at birth and was diagnosed with oculocutaneous albinism at age 3 months. Although bruising and bleeding after trauma were noted in childhood, he was not diagnosed with HPS until age 16 years, when laboratory studies showed absence of platelet dense granules. There was no renal or lung disease. The third was a 13-year-old girl of German and Dutch descent who had rotary nystagmus in infancy and was diagnosed with oculocutaneous albinism. She had global delayed development and easy bruising. Platelet storage pool deficiency and absence of dense bodies were noted at age 4 years. The fourth patient, a 52-year-old Italian man, also had rotary nystagmus at birth and bruising in childhood. He was diagnosed at age 44 years only when he was found to have gastrointestinal symptoms and oculocutaneous albinism. Laboratory studies showed iron-deficiency anemia and low vitamin B12. There was no interstitial lung disease or renal involvement. Huizing et al. (2009) concluded that patients with HPS6 appear to have clinical features similar to those of other BLOC2-deficient patients, that is, patients with HPS3 (614072) and HPS5 (614074).
In a 39-year-old Belgian woman with HPS, Zhang et al. (2003) identified a homozygous 4-bp deletion (607522.0001) in the HPS6 gene.
Huizing et al. (2009) identified homozygous or compound heterozygous mutations (607522.0003-607522.0007) in the HPS6 gene ... In a 39-year-old Belgian woman with HPS, Zhang et al. (2003) identified a homozygous 4-bp deletion (607522.0001) in the HPS6 gene. Huizing et al. (2009) identified homozygous or compound heterozygous mutations (607522.0003-607522.0007) in the HPS6 gene in 4 unrelated patients with Hermansky-Pudlak syndrome. All mutations except 1 resulted in a truncated protein. The phenotype was characterized by early-onset nystagmus, oculocutaneous albinism, and a mild bleeding diathesis, but no pulmonary fibrosis, granulomatous colitis, or renal involvement. However, 2 patients had gastrointestinal symptoms. In vitro cellular studies performed on patient melanocytes indicated aberrant cytoplasmic distribution patterns of melanogenic proteins and increased trafficking of TYRP1 (115501) through the plasma membrane, indicating a defect in lysosomal-related organelles.