Hermansky–Pudlak syndrome

Signs and symptoms

Individuals with Hermansky–Pudlak syndrome have varying amounts of skin pigment due to albinism, leading to eye problems such as photophobia, strabismus, and nystagmus, as well as impaired vision. Bleeding disorders arise from platelet dysfunction, causing easy bruising and bleeding. The syndrome also involves accumulation of ceroid in body tissues, damaging the lungs and kidneys, and is associated with granulomatous colitis and pulmonary fibrosis.

Causes

HPS can be caused by mutations in at least 11 different genes that encode subunits of protein complexes involved in the biogenesis of lysosome related organelles. These include HPS1, HPS3, HPS4, HPS5, HPS6, HPS7, HPS8, HPS9, HPS10, and HPS11.

HPS type 2, which includes immunodeficiency, is caused by mutation in the AP3B1 gene, and HPS type 7 may result from a mutation in the gene coding for dysbindin protein. The syndrome is inherited as an autosomal recessive trait, meaning a person must inherit two copies of the defective gene to develop the disorder. Carriers, with one normal and one defective gene, usually show no symptoms, and each pregnancy of two carriers has a 25 percent risk of an affected child.

Diagnosis

Diagnosis of HPS is established by clinical findings of hypopigmentation of the skin and hair, characteristic eye findings, and demonstration of absent dense bodies on whole mount electron microscopy of platelets. Molecular genetic testing of the HPS1 gene is available clinically for individuals from northwestern Puerto Rico, and testing of the HPS3 gene is available for those of central Puerto Rican or Ashkenazi Jewish heritage. Sequence analysis for mutations in HPS1 and HPS4 is available clinically, while diagnosis of other types is available on a research basis only.

Treatment

There is no cure for HPS. Treatment for chronic hemorrhages includes therapy with vitamin E and the antidiuretic dDAVP.

Preoperative pulmonology consultation is needed due to potential postoperative pulmonary complications, and hematology consultation is advisable before elective ocular surgeries. If platelet aggregation improves with desmopressin, it may be given preoperatively, though plasmapheresis is sometimes needed. Ophthalmologists should avoid retrobulbar blocks, and general endotracheal anesthesia may be beneficial.

Did You Know?

• The major complication of most forms of HPS is pulmonary fibrosis, which typically exhibits in patients ages 40–50 years and is the usual cause of death.
• HPS is one of the rare lung diseases currently being studied by The Rare Lung Diseases Consortium.