Hermansky–Pudlak syndrome

Overview

Hermansky–Pudlak syndrome (HPS) is a rare, inherited multisystem disorder characterized by a combination of oculocutaneous albinism, a bleeding tendency due to platelet dysfunction, and in some cases, serious complications such as pulmonary fibrosis, granulomatous colitis, or kidney disease. First described in 1959 by Drs. Hermansky and Pudlak in Puerto Rican patients, HPS is most prevalent in individuals of Puerto Rican and Swiss descent. The syndrome results from genetic mutations that affect the formation and function of lysosome-related organelles, including melanosomes and platelet dense granules.

Causes

Hermansky–Pudlak syndrome is caused by mutations in any one of at least 11 different genes (HPS1 through HPS11), all of which are involved in the biogenesis of lysosome-related organelles. These genetic mutations disrupt the normal production and trafficking of proteins necessary for pigmentation and platelet function. The disorder is inherited in an autosomal recessive pattern, meaning an individual must inherit two defective copies of the gene (one from each parent) to develop the syndrome.

Symptoms

The clinical features of HPS vary depending on the genetic subtype, but common symptoms include:

• Oculocutaneous albinism: Light-colored skin, hair, and eyes; reduced visual acuity; nystagmus; and photophobia

• Bleeding diathesis: Easy bruising, prolonged bleeding after injury or surgery, heavy menstrual bleeding due to defective platelet function

• Pulmonary fibrosis: Progressive scarring of lung tissue, typically seen in HPS-1 and HPS-4 subtypes, leading to chronic cough and shortness of breath

• Inflammatory bowel disease: Colitis resembling Crohn’s disease, seen in some subtypes (especially HPS-1 and HPS-4)

• Kidney disease or granulomatous disease: Rare but possible, depending on subtype

The severity of symptoms can vary widely, even among individuals with the same subtype.

Diagnosis

Diagnosis of Hermansky–Pudlak syndrome is based on clinical findings, laboratory tests, and genetic analysis. Diagnostic steps include:

• Clinical evaluation: Identification of albinism and bleeding symptoms

• Platelet function tests: Show absent or reduced dense granules and impaired aggregation

• Electron microscopy: Confirms the absence of dense granules in platelets

• Genetic testing: Identifies mutations in one of the HPS genes to confirm diagnosis and subtype

Additional tests such as pulmonary function tests, high-resolution chest CT, or colonoscopy may be performed to assess complications like lung fibrosis or colitis.

Treatment

There is no cure for Hermansky–Pudlak syndrome, and treatment focuses on symptom management and prevention of complications. Management includes:

• Bleeding management:

  • Avoidance of aspirin and other blood-thinning medications

  • Use of desmopressin (DDAVP) or platelet transfusions before surgeries

• Vision support: Low vision aids, sunglasses, and regular ophthalmologic care

• Pulmonary fibrosis: Supportive oxygen therapy, antifibrotic agents in research settings, and lung transplantation in advanced cases

• Colitis management: Anti-inflammatory medications, immunosuppressants, or surgical interventions as needed

• Genetic counseling: For affected families and carrier detection

Regular follow-up with specialists such as hematologists, pulmonologists, gastroenterologists, and ophthalmologists is essential for comprehensive care.

Prognosis

The prognosis of Hermansky–Pudlak syndrome depends on the genetic subtype and the severity of organ involvement. Individuals with mild forms may live normal lifespans with manageable symptoms. However, those with complications such as pulmonary fibrosis or severe colitis may experience significant morbidity and reduced life expectancy. Early diagnosis, symptom monitoring, and multidisciplinary care can improve quality of life and outcomes for affected individuals.