Hermansky-Pudlak syndrome

Hermansky-Pudlak syndrome: Abbreviated HPS. A genetic disorder characterized by albinism (with lack of pigment in the skin or eye), bruising and prolonged bleeding (due to defective blood platelets), and fibrosis of the lungs. There is occasionally also inflammatory bowel disease and impaired kidney function. All HPS patients suffer from varying degrees of albinism. The lack of pigment in the eye impairs their vision and often leads to involuntary rhythmic eye movements called nystagmus. The most serious health problems in HPS are the tendency to bruise easily and bleed and the progressive deterioration in lung function.

The reason HPS patients bleed too easily is that their blood platelets are deficient in so-called dense bodies. These subcellular organelles release their contents to make other platelets stick together and form a clot. Without dense bodies, the time needed for a clot to form is abnormally slow. Women with HPS may therefore need medical intervention during their menstrual cycles or at childbirth. HPS patients are advised to avoid blood anticoagulants such as aspirin. Drugs are needed to prevent excessive bleeding during dental extractions and other surgical procedures. Inflammatory bowel disease with the onset of symptoms between 10 and 30 years of age can complicate HPS and usually responds poorly to therapy. The lung problems in HPS begin with restrictive disease and then progress inexorably to death, usually in the fourth or fifth decade.

HPS patients have a biochemical storage disorder. They accumulate a fatty product called ceroid lipofuscin. This causes inflammation in tissues such the lungs. Prolonged inflammation leads to fibrosis, which in the case of the lung impairs its ability both to expel air and to exchange carbon dioxide for oxygen.

HPS is inherited as an autosomal recessive condition. HPS occurs in many countries. It is especially common in certain areas in the Swiss Alps and Puerto Rico. In NW Puerto Rico, 1 in every 1800 individuals is affected with HPS and 1 in 21 persons carries the HPS gene. HPS is genetically heterogenous. It is not a single genetic entity. Mutations in different genes on different chromosomes are now known to lead to HPS. Gene loci for HPS have been identified on chromosomes 3, 5 and 10. Puerto Ricans with HPS have been found to have mutations in the HPS1 gene and, less often, in the HPS3 gene. Only half of individuals with HPS not from Puerto Rico have mutations in HPS1 and very few do in HPS3; and a number have mutations in another locus, HPS4.

Patients with HPS2 have mutations in a protein called AP-3, which is involved in directing the movement of proteins inside cells. AP-3 is needed by T cells to kill infected cells. T cells deficient in AP-3 due to HSP-2 cannot kill target cells. The lytic granules required for killing fail to move towards the contact site between the T cell and the target cell. AP-3 therefore appears to be involved in mediating granule movement inside killer T cells.

The syndrome was first described in 1959 and is named after its discoverers, the Czech internists F. Hermansky and P. Pudlak who described 2 unrelated albinos with a lifelong bleeding tendency and peculiar pigmented cells in the bone marrow. One patient was male and the other female, both 33 years old.

HPS is also known as albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells and as delta-storage pool disease.