Hermansky Pudlak Disease background

In 1959, Hermansky and Pudlak described 2 patients with oculocutaneous albinism (OCA) who had bleeding diathesis. Both patients had pulmonary disease.

Hermansky-Pudlak syndrome (HPS) is a heterogeneous group of autosomal recessive disorders characterized by tyrosinase-positive oculocutaneous albinism (Ty-pos OCA), bleeding tendency diathesis, and systemic complications associated to lysosomal dysfunction, such as pulmonary fibrosis. There are several types of HPS. In Puerto Rico, both type one (HPS type 1) and type three (HPS type 3) have been described.

Causes

HPS is a group of autosomal recessive disorders. Therefore, consanguinity and geographical isolation increases the risk of affected offspring. Pseudodominance has been reported in the northwestern quarter of Puerto Rico, because of patients with the syndrome who marry carriers of the HPS genes in geographically isolated regions.

Seven genes may lead to HPS in humans. Fukai and coworkers identified an HPS gene, located in chromosome region 10q23.1-23.3 by using a positional cloning approach. Genetic analysis of Puerto Rican patients identified a 16-base pair duplication/frameshift within exon 15. This results in a frameshift at codon Pro 496. This gene is called the HPS-1 gene.

Puerto Rican patients with HPS type 3 have all been homozygous for a 3,904-bp deletion in the HPS-3 gene, as described by Anikster and coworkers. However, further studies have shown evidence for locus heterogeneity in Puerto Ricans with the syndrome. Bailin and coworkers suggest that mutations in the adaptor-related code complex (termed AP-3) subunits may lead to some forms of HPS.3 The AP-3 complex facilitates transport of vesicles from the trans-Golgi network and endosomal compartments. AP-3 interacts with tyrosine signals on proteins of lysosomes and other intracellular organelles.

Frequency

The various types of HPS are rare genetic diseases worldwide. However, HPS type 1 is the most common single gene disorder in Puerto Rico, being most prevalent in the northwestern quadrant of the island.

Epidemiologic studies report that in this region, 1 out of 1,800 persons have the syndrome. In this area, approximately 1 out of 21 persons carry the gene encoding for HPS. On the other hand, HPS type 3 is more prevalent in the central mountainous region of the island.

In Puerto Rico, 5 out of 6 patients with OCA have HPS. For this reason, in Puerto Rico, a patient with OCA has HPS until proven otherwise. If a patient in the continental United States has OCA and Puerto Rican family members, HPS must be ruled out.

Patients with HPS have been reported in other nations, including Holland, the United Kingdom, and Mexico. Further, it has been reported among Jews.

Donate to the cause

Lung Disease

HPS also includes lung disease. Many with HPS have pulmonary fibrosis, which means that the tissue of the lung scars, and restricts the inflation of the lungs.

The lung problems tend to worsen with time. Spirometry, which involves measuring air flow as a person blows into a machine, may show a problem before any chest x-ray changes appear.

Pulmonary Fibrosis

A more common problem in Hermansky-Pudlak syndrome is lung disease. It seems that it may be dependent on which gene mutation of HPS is present. It is particularly prevalent in those individuals that are of Puerto Rican ancestry.

Under investigation is the possibility that the accumulation of ceroid is associated with an inflammatory response in the lungs which eventfully scars the lung tissue and it losses its ability to expand and contract with the mechanisms of breathing. It begins to restrict the inflation of the lungs.

Symptoms of Pulmonary Fibrosis

When lungs become affected, shortness of breath and abnormal fatigue with exertion might be a sign. One way it can be followed is through Pulmonary Function Tests (PFT) and the result of the Forced Vital Capacity (FVC).

Visual Impairment

The visual impairment inherent in HPS persons is the same as in other types of albinism. It is a result of the lack of pigment during eye development. This has a consequence of decreased acuity which is frequently severe enough to be legal blindness, photophobia (light sensitivity), strabismus (crossed eyes), and nystagmus (involuntary movement of the eyes).

Information Obtained From

• eMedicine.com
• Albinism.org
• hpsNetwork.org