Hermansky–Pudlak syndrome

Hermanskyâ€"Pudlak syndrome (HPS) is a rare autosomal recessive disorder which results in oculocutaneous albinism (decreased pigmentation), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin).

It is considered to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800. Many of the clinical research studies on the disease have been conducted in Puerto Rico.

There are eight classic forms of the disorder, based on the genetic mutation from which the disorder stems. A ninth type has also been described. This last type is due to a mutation in the gene Pallidin (PLDN).

Prognosis

The course of HPS has been mild in rare instances of the disorder, however, the general prognosis is still considered to be poor.

The disease can cause dysfunctions of the lungs, intestine, kidneys or heart. The major complication of most forms of the disorder is pulmonary fibrosis, which typically exhibits in patients ages 40â€"50 years. This is a fatal complication seen in many forms of HPS, and is the usual cause of death from the disorder. HPS patients who develop pulmonary fibrosis typically have type 1 or type 4.

Diagnosis

The diagnosis of HPS is established by clinical findings of hypopigmentation of the skin and hair, characteristic eye findings, and demonstration of absent dense bodies on whole mount electron microscopy of platelets. Molecular genetic testing of the HPS1 gene is available on a clinical basis for individuals from northwestern Puerto Rico. Molecular testing of the HPS3 gene is available on a clinical basis for individuals of central Puerto Rican or Ashkenazi Jewish heritage. Sequence analysis is available on a clinical basis for mutations in HPS1 and HPS4. Diagnosis of individuals with other types of HPS is available on a research basis only.

Causes

HPS can be caused by mutations in several genes: HPS1, HPS3, HPS4, HPS5, HPS6 and HPS7.

HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in the AP3B1 gene.

HPS type 7 may result from a mutation in the gene coding for dysbindin protein.

Hermanskyâ€"Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP, responsible for this disorder is located on the long arm of chromosome 10 (10q2). Some research suggests that an abnormality of lysosomal function may be responsible for the development of the disease. HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1 and BLOC1S3 are associated with Hermanskyâ€"Pudlak syndrome.

In autosomal recessive disorders, the condition does not appear unless a person inherits two copies of the defective gene responsible for the disorder, one copy coming from each parent. If an individual receives one normal gene and one gene for the disorder, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.

Symptoms

There are three main disorders caused by Hermanskyâ€"Pudlak syndrome, which result in these symptoms:

• Albinism and eye problems: Individuals will have varying amounts of skin pigment (melanin). Because of the albinism there are eye problems such as light sensitivity (photophobia), strabismus (crossed eyes), and nystagmus (involuntary eye movements). Hermanskyâ€"Pudlak syndrome also impairs vision.
• Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.
• Cellular storage disorders: The syndrome causes a wax-like substance (ceroid) to accumulate in the body tissues and cause damage, especially in the lungs and kidneys.
• Is associated with Granulomatous Colitis.

It also associated with Pulmonary Fibrosis, a fatal lung disease.

Treatment

While there is no cure for HPS, treatment for chronic hemorrhages associated with the disorder includes therapy with vitamin E and the antidiuretic dDAVP.

Considerations for patients

A preoperative pneumologist consultation is needed. The anesthesia team should be aware that patients may have postoperative pulmonary complications as part of the syndrome.

Preoperative hematology consultation is advisable prior to elective ocular surgeries. Since patients with the syndrome have bleeding tendencies, intraoperative, perioperative, and postoperative hemorrhages should be prevented and treated. If platelet aggregation improves with desmopressin, it may be administered in the preoperative period. However, sometimes plasmapheresis is needed in the perioperative period.

Ophthalmologists should try to avoid retrobulbar blocks in patients with the syndrome. Whenever possible, patients with HPS may benefit from general endotracheal anesthesia. Phacoemulsification may help prevent intraoperative and postoperative bleeding in patients with the syndrome. Prolonged bleeding has been reported following strabismus surgery in patients with the syndrome.

Eponym

It is named for Frantisek Hermansky (1916â€"1980) and Paulus Pudlak (1921â€"1984).

See also

• Biogenesis of lysosome-related organelles complex 1
• List of cutaneous conditions

References

External links

• GeneReviews/NCBI/NIH/UW entry on Hermansky-Pudlak Syndrome
• Hermanskyâ€"Pudlak Syndrome Network
• NOAH/albinism.org information about HPS

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