Interdisciplinary approach to diagnosis of life-threatening form of albinism: Germanic-Pudlac syndrome case type 1

The Hermansky-Pudlak syndrome (OMIM#203300) is a hereditary genetically heterogeneous disease with an autosomal recessive type of inheritance. There are 11 clinical-genetic subtypes with similar clinical manifestations, but some type may difference with each other clinically. The most common is type 1 Hermansky-Pudlak syndrome. Purpose: Describe the features of the clinical picture and diagnosis of Hermansky-Pudlak syndrome type 1. Materials and methods: complex clinic-instrumental and molecular-genetic results from 2 patients from one family with incoming diagnosis of albinism are used. Result: An interdisciplinary approach to the diagnosis of albinism and a step-by-step molecular-genetic study help to verify the clinical-genetic diagnosis in a family. The clinical case demonstrated clinical polymorphism within one family. Two patients have similar dermatological and ophthalmological clinical picture, but have difference in bronchopulmonary system and the blood system. Probang-female has a history of prolonged repeated bleeding, coagulogram changes, obstructive bronchitis, albino phenotype and eyes failure. Her brother has a similar albino phenotype and eyes failure. The pathogenic variant NM_000195.5: c.1189del was revealed in a homozygous state in 13 exon of the HPS1 gene and Hermansky-Pudlak syndrome type 1 was confirmed by molecular analysis. Conclusion: On the example of this clinical observation of a family with Hermansky-Pudlak syndrome 1 type features of differential diagnosis of albinic states are shown, it is noted that complex examination of patients is necessary, molecular-diagnostics genetic analysis and constant follow up of a hematologist, ophthalmologist, pulmonologist, allergologist, dermatologist, gastroenterologist, geneticist and pediatrician.

Hermansky-Pudlak syndrome type 1, oculocutaneous albinism, hemorrhagic syndrome, clinical polymorphism, genetic polymorphism

1. De Jesus Rojas W., Young L. R. Hermansky-Pudlak Syndrome. Semin Respir Crit Care Med. 2020 Apr;41(2):238-246. doi: 10.1055/s-0040-1708088.

2. Yu J., He X., Wei A., Liu T. et al. HPS1 Regulates the Maturation of Large Dense Core Vesicles and Lysozyme Secretion in Paneth Cells. Front Immunol. 2020 Nov 5;11:560110. doi: 10.3389/fimmu.2020.560110.

3. Zhurkova N.V., Vashakmadze N. D., Suhanova N. V. et al. Hermansky-Pudlak Syndrome Type 6 Accompanied with Bowel Vascular Malformation: Clinical Case. Voprosy sovremennoi pediatrii - Current Pediatrics. 2021;20(6S): 595-601. (In Russ). doi: 10.15690/vsp.v20i6S.2368.

4. Huizing M, Malicdan MCV, Gochuico BR, et al. Hermansky-Pudlak Syndrome. In: GeneReviews® [Internet]. Adam MP, Ardinger HH, Pagon RA, et al., eds. Seattle (WA): University of Washington, Seattle; 1993-2021. (Available online: https://www.ncbi.nlm.nih.gov/books/NBK1287. Accessed on December 07, 2021.)

5. Chiang P.W., Oiso N., Gautam R., Suzuki T., Swank R. T., Spritz R. A. The Hermansky-Pudlak syndrome 1 (HPS1) and HPS4 proteins are components of two complexes, BLOC-3 and BLOC-4, involved in the biogenesis of lysosome-related organelles. J Biol Chem. 2003 May 30;278(22):20332-7. doi: 10.1074/jbc.M300090200.

6. Hermansky F., Pudlak P. Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies. Blood. 1959;14 (2): 162-169. doi: 10.1182/blood.V14.2.162.162.

7. Santos Malave G., Izquierdo N. J., Sanchez N. P. Dermatologic manifestations in patients with the Hermansky-Pudlak syndrome types 1 and 3. Orphanet J Rare Dis. 2022 Jul 30;17(1):305. doi: 10.1186/s13023-022-02464-w.

8. Marakhonov A. V., Voskresenskaya A. A., Ballesta M. J. et al. Expanding the phenotype of CRYAA nucleotide variants to a complex presentation of anterior segment dysgenesis. Orphanet J Rare Dis. 2020 Aug 13;15(1):207. doi: 10.1186/s13023-020-01484-8.

9. Oh J., Ho L., Ala-Mello S., Amato D. et al. Mutation analysis of patients with Hermansky-Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity. Am J Hum Genet. 1998 Mar;62(3):593-8. doi: 10.1086/301757.

10. Vincent L. M., Adams D., Hess R. A. et al. Hermansky-Pudlak syndrome type 1 in patients of Indian descent. Mol Genet Metab. 2009 Jul;97(3):227-33. doi: 10.1016/j.ymgme.2009.03.011.

11. Ito S., Suzuki T., Inagaki K., Suzuki N. et al. High frequency of Hermansky-Pudlak syndrome type 1 (HPS1) among Japanese albinism patients and functional analysis of HPS1 mutant protein. J Invest Dermatol. 2005 Oct;125(4):715-20. doi: 10.1111/j.0022-202X.2005.23884.x.