Hermansky-Pudlak syndrome

background

Hermansky-Pudlak syndrome (HPS) belongs to a group of disorders known as albinism. Albinism is characterized by decreased or absent pigment (coloring) in the skin, hair, and iris of the eyes. In some cases, albinism includes other eye problems, such as decreased visual clearness, sensitivity to light, involuntary eye movements, problems with the iris, and decreased pigment in the retina on the back of the eye.
Albinism is caused by mutations or defects in genes that provide instructions for making the pigment melanin, a material that changes the color of light it reflects and provides color to hair, skin, and eyes. Unlike some types of albinism, in which melanin is completely absent, people with HPS do produce some melanin, so this may be a less severe type of the disease. HPS includes a bleeding tendency and a predisposition to lung disease. HPS may also include inflammatory bowel disease or kidney disease.
There are eight types of HPS, each of which is caused by a different genetic mutation or defect. HPS is inherited, or passed down among family members, as an autosomal recessive trait. Individuals receive two copies of most genes, one from the mother and one from the father. To inherit an autosomal recessive trait, an individual must inherit two defective copies of the causative gene. Individuals who inherit only one copy of the defective gene are called carriers. Carriers generally do not have any symptoms but may pass on the disorder to their children.
Genes that may lead to HPS in humans include the HPS1,HPS2 (AP3B1), HPS3, HPS4, HPS5, HPS6, and HPS7 genes, which are involved in vesicle formation within cells. Vesicles transport substances within the cell that allow for normal functioning.
Symptoms of HPS vary widely among patients and may include bleeding problems, such as easy bruising, nosebleeds, and extended bleeding times. Improper handling of ceroid, a naturally occurring fatty substance, can result in pulmonary fibrosis, inflammatory bowel disease, kidney disease, and eye problems resulting from a lack of pigmentation in the eye, leading to light sensitivity, crossed eyes, and involuntary eye movements.
Overall prevalence of HPS is about one in 500,000-1,000,000 in the general population. The prevalence of HPS in Puerto Rico, however, is estimated at about one in 1,800-2,000. HPS type 1 is the most common single-gene disorder in Puerto Rico. Single-gene disorders are very rare genetic diseases. HPS type 3 is more common in inland Puerto Rico than in coastal areas. The prevalence of all types of carriers in Puerto Rico is about one in 21. This disease is most common in Puerto Rico, but it has been reported in Switzerland, Japan, and other countries. Cases of Ashkenazi Jews with mild symptoms and mutations in the HPS3 gene have been reported. HPS appears to affect males and females in equal numbers.
About 70% of people with HPS die from complications of the disorder, including lung problems, excessive bleeding, or problems with the intestine, liver, or kidneys. Life expectancy is typically about 40-50 years.

Related Terms

Albinism, albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells, autosomal recessive inheritance, bleeding tendency diathesis, cardiomyopathy, colitis, delta storage pool disease, HPS, HPS1, HPS2, HPS3, HPS4, HPS5, HPS6, HPS7, HPS type 1, HPS type 2, HPS type 3, HPS type 4, HPS type 5, HPS type 6, HPS type 7, HPS type 8, pulmonary fibrosis, Ty-pos OCA, tyrosinase-positive oculocutaneous albinism.

types of the disease

General: There are eight types of Hermansky-Pudlak syndrome (HPS), each of which is caused by a different genetic mutation or defect. Information on the differences between these types of HPS is currently lacking.
HPS type 1: HPS type 1 is caused by mutations in the HPS1 gene, which provides instructions for making the HPS 1 protein (HPS1). This protein is likely involved in the normal function and development of the organelles (tiny organs) found in cells. HPS type 1 has been found among people of Puerto Rican, Swiss, Japanese, and Irish heritage.
HPS type 2: HPS type 2 is caused by mutations in the AP3B1 (or HPS2) gene, which provides instructions for making the AP-3 complex subunit beta-1 protein. The exact function of this protein is currently unknown. HPS type 2 has been associated with immune system problems.
HPS type 3: HPS type 3 is caused by mutations in the HPS3 gene, which provides instructions for making the HPS 3 protein (HPS3), whose function is currently unknown. Hair and skin color may be darker in individuals with this type of HPS.
HPS type 4: HPS type 4 is caused by mutations in the HPS4 gene, which provides instructions for making the HPS 4 protein (HPS4), whose exact function is currently unknown.
HPS type 5: HPS type 5 is caused by mutations in the HPS5 gene, which provides instructions for making the HPS 5 protein (HPS5), whose exact function is currently unknown.
HPS type 6: HPS type 6 is caused by mutations in the HPS6 gene, which provides instructions for making the HPS 6 protein (HPS6), whose exact function is currently unknown.
HPS type 7: HPS type 7 is caused by mutations in the DTNBP1 gene, which provides instructions for making the dysbindin protein. This protein may be involved in the development of organelles called lysosomes, which contain digestive enzymes and serve as a cleanup function within the cell by digesting organelles that are no longer functioning properly, or viruses and bacteria that may invade the cell.
HPS type 8: HPS type 8 is caused by mutations in the BLOC1S3 gene, which provides instructions for making the biogenesis of lysosome-related organelles complex-1 subunit 3 protein. This protein serves a similar function to the dysbindin protein in HSP type 7, in that it may be involved in the development of lysosomes.