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Hermansky-Pudlak syndrome(HPS)

MedGen UID:
36313
Concept ID:
C0079504
Disease or Syndrome
Synonyms: Albinism with hemorrhagic diathesis and pigmented reticuloendothelial cells; HPS
SNOMED CT: Hermansky-Pudlak syndrome (9311003); Albinism with hemorrhagic diathesis (9311003); Alpha storage pool disease (9311003); Hermansky Pudlak syndrome (9311003)
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Related genes: BLOC1S3, HPS4, HPS3, DTNBP1, HPS6, BLOC1S6, HPS5, AP3D1, AP3B1, HPS1
 
Monarch Initiative: MONDO:0019312
OMIM® Phenotypic series: PS203300
Orphanet: ORPHA79430

Disease characteristics

Excerpted from the GeneReview: Hermansky-Pudlak Syndrome
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, and/or immunodeficiency. Ocular findings include nystagmus, reduced iris pigment, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), and strabismus in many individuals. Hair color ranges from white to brown; skin color ranges from white to olive and is usually at least a shade lighter than that of other family members. The bleeding diathesis can result in variable degrees of bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and/or other surgeries. Pulmonary fibrosis, colitis, and/or neutropenia have been reported in individuals with pathogenic variants in some HPS-related genes. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early 30s and can progress to death within a decade. Granulomatous colitis is severe in about 15% of affected individuals. Neutropenia and/or immune defects occur primarily in individuals with pathogenic variants in AP3B1 and AP3D1. [from GeneReviews]
Authors:
Wendy J Introne  |  Marjan Huizing  |  May Christine V Malicdan, et. al.   view full author information

Additional description

From MedlinePlus Genetics
Hermansky-Pudlak syndrome is a disorder characterized by a condition called oculocutaneous albinism, which causes abnormally light coloring (pigmentation) of the skin, hair, and eyes. Affected individuals typically have fair skin and white or light-colored hair. People with this disorder have a higher than average risk of skin damage and skin cancers caused by long-term sun exposure. Oculocutaneous albinism reduces pigmentation of the colored part of the eye (iris) and the light-sensitive tissue at the back of the eye (retina). Reduced vision, rapid and involuntary eye movements (nystagmus), and increased sensitivity to light (photophobia) are also common in oculocutaneous albinism. In Hermansky-Pudlak syndrome, these vision problems usually remain stable after early childhood.

People with Hermansky-Pudlak syndrome also have problems with blood clotting (coagulation) that lead to easy bruising and prolonged bleeding.

Some individuals with Hermansky-Pudlak syndrome develop breathing problems due to a lung disease called pulmonary fibrosis, which causes scar tissue to form in the lungs. The symptoms of pulmonary fibrosis usually appear during an individual's early thirties and rapidly worsen. Individuals with Hermansky-Pudlak syndrome who develop pulmonary fibrosis often do not live for more than a decade after they begin to experience breathing problems.

There are nine different types of Hermansky-Pudlak syndrome, which can be distinguished by their signs and symptoms and underlying genetic cause. Types 1 and 4 are the most severe forms of the disorder. Types 1, 2, and 4 are the only types associated with pulmonary fibrosis. Individuals with type 3, 5, or 6 have the mildest symptoms. Little is known about the signs, symptoms, and severity of types 7, 8, and 9.

Other, less common features of Hermansky-Pudlak syndrome include inflammation of the large intestine (granulomatous colitis) and kidney failure.  https://medlineplus.gov/genetics/condition/hermansky-pudlak-syndrome

Professional guidelines

PubMed

Zamani R, Shahkarami S, Rezaei N
Allergol Immunopathol (Madr) 2021;49(2):178-190. Epub 2021 Mar 1 doi: 10.15586/aei.v49i2.61. PMID: 33641308
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Respir Investig 2021 Jan;59(1):8-33. Epub 2020 Jul 2 doi: 10.1016/j.resinv.2020.04.004. PMID: 32622842
Feliciano NZ, Rivera E, Agrait E, Rodriguez K
J Dent Child (Chic) 2006 Jan-Apr;73(1):51-6. PMID: 16734315

Suggested Reading

Recent clinical studies

Etiology

Banushi B, Simpson F
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Huizing M, Malicdan MCV, Wang JA, Pri-Chen H, Hess RA, Fischer R, O'Brien KJ, Merideth MA, Gahl WA, Gochuico BR
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Diagnosis

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Grønskov K, Ek J, Brondum-Nielsen K
Orphanet J Rare Dis 2007 Nov 2;2:43. doi: 10.1186/1750-1172-2-43. PMID: 17980020Free PMC Article

Therapy

Merideth MA, Introne WJ, Wang JA, O'Brien KJ, Huizing M, Gochuico BR
Platelets 2020 May 18;31(4):544-547. Epub 2019 Sep 5 doi: 10.1080/09537104.2019.1663810. PMID: 32436471Free PMC Article
O'Brien KJ, Introne WJ, Akal O, Akal T, Barbu A, McGowan MP, Merideth MA, Seward SL Jr, Gahl WA, Gochuico BR
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Feliciano NZ, Rivera E, Agrait E, Rodriguez K
J Dent Child (Chic) 2006 Jan-Apr;73(1):51-6. PMID: 16734315

Prognosis

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Power B, Ferreira CR, Chen D, Zein WM, O'Brien KJ, Introne WJ, Stephen J, Gahl WA, Huizing M, Malicdan MCV, Adams DR, Gochuico BR
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Clinical prediction guides

Suzuki T, Kropski JA, Chen J, Carrier EJ, Chen X, Sherrill TP, Winters NI, Camarata JE, Polosukhin VV, Han W, Rathinasabapathy A, Gutor S, Gulleman P, Sabusap C, Banovich NE, Tanjore H, Freeman ML, Tada Y, Young LR, Gokey JJ, Blackwell TS, West JD
Am J Respir Crit Care Med 2022 Sep 1;206(5):596-607. doi: 10.1164/rccm.202106-1503OC. PMID: 35728047Free PMC Article
Kuht HJ, Maconachie GDE, Han J, Kessel L, van Genderen MM, McLean RJ, Hisaund M, Tu Z, Hertle RW, Gronskov K, Bai D, Wei A, Li W, Jiao Y, Smirnov V, Choi JH, Tobin MD, Sheth V, Purohit R, Dawar B, Girach A, Strul S, May L, Chen FK, Heath Jeffery RC, Aamir A, Sano R, Jin J, Brooks BP, Kohl S, Arveiler B, Montoliu L, Engle EC, Proudlock FA, Nishad G, Pani P, Varma G, Gottlob I, Thomas MG
Ophthalmology 2022 Jun;129(6):708-718. Epub 2022 Feb 11 doi: 10.1016/j.ophtha.2022.02.010. PMID: 35157951Free PMC Article
Koike S, Yamasaki K
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Huizing M, Malicdan MCV, Wang JA, Pri-Chen H, Hess RA, Fischer R, O'Brien KJ, Merideth MA, Gahl WA, Gochuico BR
Hum Mutat 2020 Mar;41(3):543-580. Epub 2020 Jan 23 doi: 10.1002/humu.23968. PMID: 31898847Free PMC Article
Wei ML
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Recent systematic reviews

Ma YJ, Zhang Q, Wang CX, Wu W
Eur Rev Med Pharmacol Sci 2022 Nov;26(22):8411-8424. doi: 10.26355/eurrev_202211_30377. PMID: 36459024
Hutchison DM, Duffens A, Yale K, Park A, Cardenas K, Mesinkovska NA
J Eur Acad Dermatol Venereol 2022 Apr;36(4):536-546. Epub 2021 Dec 31 doi: 10.1111/jdv.17877. PMID: 34919300
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Int J Gynaecol Obstet 2021 Sep;154(3):412-426. Epub 2021 Mar 9 doi: 10.1002/ijgo.13632. PMID: 33521972
Klay D, Hoffman TW, Harmsze AM, Grutters JC, van Moorsel CHM
Eur Respir Rev 2018 Sep 30;27(149) Epub 2018 Jul 11 doi: 10.1183/16000617.0135-2017. PMID: 29997245Free PMC Article

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