Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome (HPS) is a rare, hereditary disorder that consists of two characteristics: decreased pigmentation (albinism) with visual impairment, and blood platelet dysfunction with prolonged bleeding. Some patients have lung fibrosis, colitis, or an abnormal storage of a fatty-like substance (ceroid lipofuscin) in various tissues of the body.

The first symptoms of HPS often include easy bruising, bleeding gums, nose bleeds, and excessive bleeding after surgery or accidents. The classic symptoms of Hermansky-Pudlak syndrome include the lack of color (pigmentation) in the skin, hair, and eyes (oculocutaneous albinism), and dysfunction of blood platelets leading to prolonged bleeding (storage pool-deficient platelets).

The skin, hair, and eyes of a person with HPS may vary in color from very pale to almost normal coloring. Eyesight is almost always impaired, commonly with visual acuities of 20/200 or worse (i.e., legally blind). The blood storage abnormality may cause excessive bleeding, especially in women during menstruation. Bleeding may become life-threatening, and aspirin makes the bleeding worse. Approximately one-sixth of HPS patients develop inflammation of the colon, with bleeding. Patients with type 1, type 2, or type 4 HPS (see below) develop a lung disease called pulmonary fibrosis that can lead to death in their thirties, forties, or fifties.

The deposits of fatty-like ceroid lipofuscin may occur within the cells of many organs such as the lungs, colon, heart, and kidneys. This by itself is not known to cause symptoms.

HPS is inherited as an autosomal recessive genetic disease. Mutations in one of 10 genes (HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, PLDN, and AP3D1) are responsible for this disorder. Research suggests that an abnormality of the formation or movement of lysosome-like vesicles may be responsible for the development of the disease. Humans inherit one gene from the father and one from the mother. In recessive disorders, the condition does not appear unless a person inherits one defective gene from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but will not show symptoms. If both parents are carriers for a recessive disorder, the risk of transmitting the disease to a child is 25 percent; the risk that a child would be a carrier for the disease is 50 percent, and a child would inherit two normal genes 25 percent of the time. The risk is the same for each pregnancy.

HPS is a rare disorder that affects males and females in equal numbers. It is most prevalent in persons from northwest Puerto Rico, where HPS affects one of every 1,800 individuals. One in 21 individuals of northwest Puerto Rican descent is believed to be carriers of the HPS type 1 gene. However, HPS does occur in other populations as well. It is the third most prevalent form of albinism.

HPS is diagnosed by the clinical features of hypopigmentation of the skin and hair, characteristic eye findings, and characteristic appearance of the blood platelets under an electron microscope. Molecular genetic testing for mutations in the HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, PLDN, and AP3D1 genes is available to confirm the diagnosis.

Treatment of HPS patients with excessive bleeding may consist of transfusions of normal blood platelets. Women with excessive menstrual bleeding (menorrhagia) can be treated with oral contraceptives. The drug desmopressin acetate (DDAVP) can also be administered to patients with acute bleeding and has proved effective for some patients with this symptom. Individuals with HPS should avoid blood anticoagulants, such as aspirin.

Patients with HPS types 1, 2, or 4 who develop pulmonary fibrosis may eventually need a lung transplant. For these individuals, platelet transfusions should be used sparingly, since multiple such transfusions can induce antibodies that could cause graft rejection.

Genetic counseling is recommended for affected individuals and their families. Other treatment is symptomatic and supportive.