Hermansky-Pudlak syndrome

Synonyms

2

Overview

Hermansky-Pudlak syndrome (HPS) is a rare disorder characterized by various degrees of albinism, bleeding due to a platelet defect and accumulation of a waxy substance in cells (lysosomal ceroid storage).

Symptoms

  • Lack of skin pigmentation
  • Lack of hair pigmentation
  • Lack of eye pigmentation
  • Rapid involuntary eye movements
  • Sensitivity to light
  • Hemorrhagic episodes
  • Mild bleeding
  • Easy bruising
  • Nosebleed
  • Restrictive lung disease
  • Ulcerative colitis
  • Albinism
  • Blood platelet defects
  • Abnormal blood clotting
  • Pulmonary fibrosis
  • Inflammatory bowel disease
  • Kidney disease
  • Impaired vision
  • Cross eyed
  • Involuntary eye movements
  • Lack of skin pigmentation
  • Lack of hair pigmentation
  • Lack of eye pigmentation
  • Rapid involuntary eye movements
  • Sensitivity to light
  • Hemorrhagic episodes
  • Mild bleeding
  • Easy bruising
  • Nosebleed
  • Restrictive lung disease
  • Ulcerative colitis
  • Albinism
  • Blood platelet defects
  • Abnormal blood clotting
  • Pulmonary fibrosis
  • Inflammatory bowel disease
  • Kidney disease
  • Impaired vision
  • Cross eyed
  • Involuntary eye movements

Causes

Oculocutaneous albinism results from autosomal recessive inheritance; ocular albinism, from an X-linked recessive trait that causes hypopigmentation only in the iris and the ocular fundus. Normally, melanocytes synthesize melanin. Melanosomes, melanin-containing granules within melanocytes, diffuse and absorb the sun's ultraviolet light, thus protecting the skin and eyes from its dangerous effects. In tyrosinase-negative albinism (the most common type), melanosomes don't contain melanin because they lack tyrosinase, the enzyme that stimulates melanin production. In tyrosinase-positive albinism, melanosomes contain tyrosine, a tyrosinase substrate, but a defect in the tyrosine transport system impairs melanin production. In tyrosinase-variable albinism (rare), an unidentified enzyme defect probably impairs synthesis of a melanin precursor. Other rare forms of albinism are Chédiak-Higashi syndrome (tyrosine-negative albinism with hematologic and neurologic manifestations); Hermansky-Pudlak syndrome (tyrosinase-positive albinism with platelet dysfunction, bleeding abnormalities, and ceroidlike inclusions in many organs); and Cross-McKusick-Breen syndrome (tyrosinase-positive albinism with neurologic involvement). In the United States, both types of albinism are more common in Blacks than in Whites. Native Americans have a high incidence of the tyrosine-positive form.

Diagnosis

The diagnosis of Hermansky-Pudlak syndrome (HPS) is established by clinical findings of oculocutaneous albinism in combination with a bleeding diathesis of variable severity.

The diagnosis of oculocutaneous albinism is established by finding hypopigmentation of the skin and hair on physical examination associated with the following characteristic ocular findings:

  • Nystagmus
  • Reduced iris pigment with iris transillumination
  • Reduced retinal pigment on fundoscopic examination
  • Foveal hypoplasia associated with significant reduction in visual acuity
  • Increased crossing of the optic nerve fibers

Source: National Center for Biotechnology Information

Prognosis

Prognosis of Hermansky-Pudlak Syndrome: 70% of patients die due to complications but mild cases can be almost asymptomatic

Treatment

Treatment of manifestations: correction of refractive errors and use of low vision aids; thrombin-soaked gelfoam for skin wounds with prolonged bleeding; DDAVP (1-desamino-8-D-arginine vasopressin) for wisdom tooth extraction and invasive procedures; platelet or red blood cell transfusions for surgery or protracted bleeding; supplemental oxygen for severe pulmonary disease; steroids, other anti-inflammatory agents and/or Remicade® for granulomatous colitis.

Prevention of secondary complications: protection of the skin from the sun; wearing a medical alert bracelet that explicitly describes the functional platelet defect; maximizing pulmonary function before development of pulmonary fibrosis by prompt treatment of pulmonary infections, immunizing with influenza and pneumococcal vaccines, and regular moderate exercise.

Surveillance: annual ophthalmologic examination; at least annual examination of the skin for solar keratoses (premalignant lesions), basal cell carcinoma, squamous cell carcinoma; annual pulmonary function testing in those over age 20 years; routine history for symptoms of colitis (e.g., cramping, increased mucus in the stool, rectal bleeding).

Agents/circumstances to avoid: aspirin-containing products, cigarette smoke.

Source: National Center for Biotechnology Information