Hermansky-Pudlak syndrome

Author: Dr Harriet Cheng, Dermatology Registrar, Greenlane Hospital, Auckland. Chief Editor: Dr Amanda Oakley, Dermatologist, Hamilton, New Zealand, June 2014.

Synonyms:

Albinism with haemorrhagic diathesis, Alpha storage pool disease, Delta storage pool disease, MIM 203300, MIM 608233, MIM 614075

Categories:

Genetic disorder

Subcategories:

Oculoutaneous albinism, Bleeding disorder, Genetics of Hermansky-Pudlak syndrome, Subtypes of Hermansky-Pudlack syndrome, Clinical features of Hermansky-Pudlak syndrome - skin, eyes and other, Platelet dysfunction in Hermansky-Pudlak syndrome, Diagnosis of Hermansky-Pudlak syndrome - electron microscopy, Treatment of Hermansky-Pudlak syndrome

ICD-10:

E70.331

ICD-11:

EC23.20

SNOMED CT:

9311003

What is Hermansky-Pudlak syndrome?

Hermanksy-Pudlak syndrome is an inherited disorder due to an abnormality of lysosome-related organelles. Ten subtypes are described. Hermanksy-Pudlak syndrome is characterised by:

Oculocutaneous albinism
Visual impairment
A tendency to bleeding.

What are lysosome-related organelles?

Lysosomes are organelles that contain substances capable of breaking down various structures such as proteins, lipids, carbohydrates and nucleic acids.

Lysosome-related organelles are structures found within specific types of cells (eg, melanocytes) that share some similarities with lysosomes. They have various functions, including involvement in processes of pigmentation, blood clotting and immunity.

What are the clinical features of Hermansky-Pudlak syndrome?

Oculocutaneous albinism

Cutaneous findings in Hermansky-Pudlak syndrome include:

Varying degrees of skin and hair colour pigmentary dilution, compared to first-degree relatives
Freckles and lentigines in sun-exposed areas
Actinic keratosis and skin cancers, especially squamous cell carcinoma.

Visual impairment

Visual disorders in Hermanksy-Pudlak syndrome include:

Photophobia (light sensitivity)
Reduced visual acuity/ refractive errors
Colour vision deficiency
Nystagmus (involuntary eye movements)
Strabismus (horizontal and vertical eye deviations)

Other symptoms

Systemic conditions associated with Hermansky-Pudlak syndrome include:

Bleeding tendency due to platelet dysfunction
Lung fibrosis, which may lead to reduced life expectancy
Granulomatous inflammation of the large bowel (similar to Crohn disease)
Kidney disease
Heart disease.

Who gets Hermansky-Pudlak syndrome?

Hermansky-Pudlak syndrome is inherited. The pattern of inheritance is autosomal recessive, so the parents of affected children rarely have the disease themselves. Each parent carries at least one copy of the disease gene. If each parent is a carrier, the chance of their offspring having Hermasnky-Pudlak syndrome is 1 in 4.

Presently (2019), at least ten different genes causing Hermansky-Pudlak syndrome have been identified. Affected genes (BLOC genes) encode components of the biogenesis of lysosomal organelles complexes.

How is Hermansky-Pudlak syndrome diagnosed?

The diagnosis of Hermansky-Pudlak syndrome may be suspected on clinical grounds when a child presents with unexpectedly light-coloured hair, skin and eyes associated with a tendency to bleeding. Electron microscopy of platelets demonstrates the virtual absence of dense bodies, which are required for normal platelet aggregation. Genetic linkage studies may identify the underlying mutation.

What is the treatment for Hermansky-Pudlak syndrome?

As this syndrome is the result of a defective gene, no curative treatment is possible.

Important management considerations include:

Sun protection measures from an early age to prevent sun damage and skin cancers
Referral for specialist assessments including dermatology, ophthalmology, respiratory and haematology
Platelet transfusions before surgical procedures
Genetic counselling for patients and their families.