Hermansky-pudlak syndrome E70.36

Hermansky and Pudlak, 1959

Rare autosomal recessive syndrome characterized by the triad:

Oculocutaneous albinism (tyrosinase positive).

Hemorrhagic diathesis due to a decrease in the number of dense-bodies in platelets (platelet storage defect).

Accumulation of ceroid and lipofuscin-like substances in various cells, tissues, so in the intestine, skin macrophages, lungs (often pulmonary fibrosis).

Autosomal recessive inherited defects of the Hermansky-Pudlak syndrome genes with consecutive defects of the HPS polypeptides or HPS proteins encoded there, which occur as membrane proteins in cytoplasmic organelles and lead to defects of cytoplasmic organelles (melanosomes, dense granulae in thrombocytes and lysosomes) due to the incorporation of ceroid.

At least 8 different gene loci (clinical pictures: HPS1-HPS8) have been described so far: gene locus HPS1 gene: 10q23.1; gene locus HPS2 gene (coding for adaptin): Chr.5; gene locus HPS3 gene: 3q24; gene locus HPS4 gene: 22q11.2-q12.2; gene locus HPS5 gene: 11p15-p13; gene locus HPS6 gene: 10q24.32.

Mutations in the HPS1 - HPS4 gene are the most common and clinically similar. The proteins encoded by HPS-1 and HPS-4 are normally colocalized in a protein complex "Biogenesis of lysosome-related organelle complex-3" (BLOC-3) and regulate biogenesis and function of lysosomes.

Interstitial pulmonary fibrosis after the age of 30 by deposition of lipofuscin-like material in alveolar macrophages.

Nephropathies may occur. Life-threatening bleeding can occur, e.g. during childbirth.

Early occurrence of actinic keratoses, basal cell carcinomas, spinocellular carcinomas. S.a.u. Albinism.

A curative therapy is not known. Only vitamin E is discussed as a preventive measure for the pulmonary fibrotic changes.

Symptomatic therapy: Consistent photoprotection because of oculocutaneous albinism (adequate clothing, sunscreen preparations, protective goggles). The patient should undergo regular medical checks: monitoring of the skin for photodamage, precancerous lesions and carcinomas, ophthalmological checks, monitoring and symptomatic treatment of ceroid deposits in organs (e.g. lungs). Control of hemorrhagic diathesis, no antiplatelet agents such as acetylsalicylic acid.

Notice. Measures that normalize bleeding time must be taken before surgery. Infusions with the vasopressin analogue desmopressin (DDAVP) (e.g. Minirin parenterally) can achieve normalization for at least 20 min.

1. Anderson PD et al (2003) Hermansky-Pudlak syndrome type 4 (HPS-4): clinical and molecular characteristics. Hum Genet 113: 10-17
2. Berz F et al (1996) Albinism, thrombopathy, zeroid storage disease - Hermansky-Pudlak syndrome. Clin Pediatric 208: 83-87
3. Clark R et al (2003) Lytic granules, secretory lysosomes and disease. Curr Opin Immunol 15: 516-521
4. Hermansky F, Pudlak P (1959) Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood 14: 162-169
5. Huizing M et al (2003) Disorders of vesicles of lysosomal lineage: the Hermansky-Pudlak syndromes. Curr Mol Med 2: 451-467
6. Mitsui H et al (2002) Does Hermansky-Pudlak syndrome predispose to systemic lupus erythematosus? Br J Dermatol 146: 908-911