Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome is characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and white or light-colored hair. Long-term sun exposure greatly increases the risk of skin damage and skin cancers. Oculocutaneous albinism reduces pigmentation of the colored part of the eye (iris) and the light-sensitive tissue at the back of the eye (retina). Oculocutaneous albinism also causes vision problems such as reduced sharpness, rapid and involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia). In Hermansky-Pudlak syndrome, these vision problems usually remain stable after early childhood.

People with Hermansky-Pudlak syndrome also have problems with blood clotting (coagulation) that lead to easy bruising and abnormal bleeding. Affected individuals have abnormal platelets, which are blood cell fragments necessary for normal blood clotting.

Some individuals with Hermansky-Pudlak syndrome develop breathing problems due to a lung disease called pulmonary fibrosis, which causes scar tissue to form in the lungs. In these people, the symptoms of pulmonary fibrosis usually appear during their early thirties and rapidly worsen. Individuals with Hermansky-Pudlak syndrome who develop pulmonary fibrosis often do not live for more than a decade after they begin to experience breathing problems.

Other, less common features of Hermansky-Pudlak syndrome include inflammation of the large intestine (colitis) and kidney failure.

There are eight different types of Hermansky-Pudlak syndrome, which can be distinguished by their pattern of signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms of all the types. Little is known about the signs, symptoms, and severity of types 7 and 8.

Read more about oculocutaneous albinism.

Hermansky-Pudlak syndrome is a rare disorder in most populations and is estimated to affect 1 in 500,000 to 1 in 1,000,000 individuals worldwide. Type 1 is more common in Puerto Rico, particularly in the northwestern part of the island where about 1 in 1,800 people are affected. Type 3 is also common in people from central Puerto Rico. Groups of affected individuals have been identified in Japan and a small village in Switzerland.

At least eight genes are associated with Hermansky-Pudlak syndrome. These genes provide instructions for making proteins that are used to make four distinct protein complexes. These protein complexes play a role in the formation and movement (trafficking) of a group of cell structures called lysosome-related organelles (LROs). LROs are very similar to compartments within the cell called lysosomes, which digest and recycle materials. However, LROs perform specialized functions and are found only in certain cell types. LROs have been identified in pigment cells (melanocytes), platelets, and lung cells.

Mutations in the genes associated with Hermansky-Pudlak syndrome prevent the formation of LROs or impair the functioning of these cell structures. The types of Hermansky-Pudlak syndrome are grouped together by protein complex. In general, mutations in genes that involve the same protein complex cause similar signs and symptoms. People with this syndrome have oculocutaneous albinism because the LROs within melanocytes cannot produce and distribute the substance that gives skin, hair, and eyes their color. Bleeding problems are caused by the absence of LROs within platelets, which affects the ability of platelets to stick together and form a blood clot. Mutations in some of the genes that cause Hermansky-Pudlak syndrome affect the normal functioning of LROs in lung cells, leading to pulmonary fibrosis.

Mutations in the HPS1 gene cause approximately 75 percent of the Hermansky-Pudlak syndrome cases from Puerto Rico. About 45 percent of affected individuals from other populations have mutations in the HPS1 gene. Mutations in the HPS3 gene are found in about 25 percent of affected people from Puerto Rico and in approximately 20 percent of cases from other areas. The other genes associated with Hermansky-Pudlak syndrome each account for a small percentage of cases of this condition.

In some people with Hermansky-Pudlak syndrome, the genetic cause of the disorder is unknown.

Read more about the HPS1 and HPS3 genes.

See a list of genes associated with Hermansky-Pudlak syndrome.

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.