Format

Send to:

Choose Destination
  • CN068492 has been replaced by C3888026, showing C3888026

Hermansky-Pudlak syndrome 8(HPS8)

MedGen UID:
854728
Concept ID:
C3888026
Disease or Syndrome
Synonyms: Hermansky-Pudlak Syndrome; HPS8
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Sources: HPO, OMIM, 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 homozygotes. In the context of medical genetics, autosomal recessive disorders manifest in homozygotes (with two copies of the mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
Autosomal recessive inheritance (HPO, OMIM, Orphanet)
 
Gene (location): BLOC1S3 (19q13.32)
OMIM®: 614077

Definition

Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties 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 GTR]

Additional description

From GeneReviews
Hermansky-Pudlak syndrome (HPS) is characterized by oculocutaneous albinism, a bleeding diathesis, and, in some individuals, pulmonary fibrosis, granulomatous colitis, or immunodeficiency. Ocular findings include reduced iris pigment with iris transillumination, reduced retinal pigment, foveal hypoplasia with significant reduction in visual acuity (usually in the range of 20/50 to 20/400), nystagmus, and increased crossing of the optic nerve fibers. Hair color ranges from white to brown; skin color ranges from white to olive and is usually a shade lighter than that of other family members. The bleeding diathesis can result in variable bruising, epistaxis, gingival bleeding, postpartum hemorrhage, colonic bleeding, and prolonged bleeding with menses or after tooth extraction, circumcision, and other surgeries. Pulmonary fibrosis, a restrictive lung disease, typically causes symptoms in the early thirties 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.  https://www.ncbi.nlm.nih.gov/books/NBK1287

Clinical features

Ocular albinism
MedGen UID:
38147
Concept ID:
C0078917
Congenital Abnormality
Albinism affecting the eye in which pigment of the hair and skin is normal or only slightly diluted. The classic type is X-linked (Nettleship-Falls), but an autosomal recessive form also exists. Ocular abnormalities may include reduced pigmentation of the iris, nystagmus, photophobia, strabismus, and decreased visual acuity.
Visual impairment
MedGen UID:
777085
Concept ID:
C3665347
Finding
Visual impairment (or vision impairment) is vision loss (of a person) to such a degree as to qualify as an additional support need through a significant limitation of visual capability resulting from either disease, trauma, or congenital or degenerative conditions that cannot be corrected by conventional means, such as refractive correction, medication, or surgery.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.
Achromasia
MedGen UID:
569448
Concept ID:
C0333913
Cell or Molecular Dysfunction
An abnormal reduction in the amount of pigmentation (reduced or absent) of skin, hair and eye (iris and retina).
Bruising susceptibility
MedGen UID:
140849
Concept ID:
C0423798
Finding
An ecchymosis (bruise) refers to the skin discoloration caused by the escape of blood into the tissues from ruptured blood vessels. This term refers to an abnormally increased susceptibility to bruising. The corresponding phenotypic abnormality is generally elicited on medical history as a report of frequent ecchymoses or bruising without adequate trauma.

Recent clinical studies

Etiology

Zhou Y, He CH, Herzog EL, Peng X, Lee CM, Nguyen TH, Gulati M, Gochuico BR, Gahl WA, Slade ML, Lee CG, Elias JA
J Clin Invest 2015 Aug 3;125(8):3178-92. Epub 2015 Jun 29 doi: 10.1172/JCI79792. PMID: 26121745Free PMC Article
Beesley RD, Robinson RD, Stewart TL
Mil Med 2008 Oct;173(10):1048-9. PMID: 19160629
Hussain N, Quezado M, Huizing M, Geho D, White JG, Gahl W, Mannon P
Clin Gastroenterol Hepatol 2006 Jan;4(1):73-80. PMID: 16431308
Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, Izquierdo NJ, Del Fierro L, Muñoz D, Molina NL, Ramírez S, Pagán-Mercado G, Ortíz I, Rivera-Caragol E, Spritz RA, Cadilla CL
J Invest Dermatol 2006 Jan;126(1):85-90. doi: 10.1038/sj.jid.5700034. PMID: 16417222Free PMC Article
Tsilou ET, Rubin BI, Reed GF, McCain L, Huizing M, White J, Kaiser-Kupfer MI, Gahl W
Ophthalmology 2004 Aug;111(8):1599-603. doi: 10.1016/j.ophtha.2003.12.058. PMID: 15288994

Diagnosis

Bryan MM, Tolman NJ, Simon KL, Huizing M, Hufnagel RB, Brooks BP, Speransky V, Mullikin JC, Gahl WA, Malicdan MC, Gochuico BR
Mol Genet Metab 2017 Apr;120(4):378-383. Epub 2017 Feb 27 doi: 10.1016/j.ymgme.2017.02.007. PMID: 28259707Free PMC Article
Kirshenbaum AS, Cruse G, Desai A, Bandara G, Leerkes M, Lee CC, Fischer ER, O'Brien KJ, Gochuico BR, Stone K, Gahl WA, Metcalfe DD
PLoS One 2016;11(7):e0159177. Epub 2016 Jul 26 doi: 10.1371/journal.pone.0159177. PMID: 27459687Free PMC Article
Zhou Y, He CH, Herzog EL, Peng X, Lee CM, Nguyen TH, Gulati M, Gochuico BR, Gahl WA, Slade ML, Lee CG, Elias JA
J Clin Invest 2015 Aug 3;125(8):3178-92. Epub 2015 Jun 29 doi: 10.1172/JCI79792. PMID: 26121745Free PMC Article
Minkin P, Bertetti R, Lindsey S, Bovino B
J Oral Maxillofac Surg 2015 Feb;73(2):219-23. Epub 2014 Sep 16 doi: 10.1016/j.joms.2014.08.037. PMID: 25579005
Lohse J, Gehrisch S, Tauer JT, Knöfler R
Hamostaseologie 2011 Nov;31 Suppl 1:S61-3. PMID: 22057877

Therapy

Zhou Y, He CH, Herzog EL, Peng X, Lee CM, Nguyen TH, Gulati M, Gochuico BR, Gahl WA, Slade ML, Lee CG, Elias JA
J Clin Invest 2015 Aug 3;125(8):3178-92. Epub 2015 Jun 29 doi: 10.1172/JCI79792. PMID: 26121745Free PMC Article
Lohse J, Gehrisch S, Tauer JT, Knöfler R
Hamostaseologie 2011 Nov;31 Suppl 1:S61-3. PMID: 22057877
Mora AJ, Wolfsohn DM
J Clin Gastroenterol 2011 Sep;45(8):700-2. doi: 10.1097/MCG.0b013e3181fd2742. PMID: 21085008
Beesley RD, Robinson RD, Stewart TL
Mil Med 2008 Oct;173(10):1048-9. PMID: 19160629
Cordova A, Barrios NJ, Ortiz I, Rivera E, Cadilla C, Santiago-Borrero PJ
Pediatr Blood Cancer 2005 Jan;44(1):51-4. doi: 10.1002/pbc.20210. PMID: 15368543

Prognosis

Carmona-Rivera C, Golas G, Hess RA, Cardillo ND, Martin EH, O'Brien K, Tsilou E, Gochuico BR, White JG, Huizing M, Gahl WA
J Invest Dermatol 2011 Dec;131(12):2394-400. Epub 2011 Aug 11 doi: 10.1038/jid.2011.228. PMID: 21833017Free PMC Article
Kloer DP, Rojas R, Ivan V, Moriyama K, van Vlijmen T, Murthy N, Ghirlando R, van der Sluijs P, Hurley JH, Bonifacino JS
J Biol Chem 2010 Mar 5;285(10):7794-804. Epub 2010 Jan 4 doi: 10.1074/jbc.M109.069088. PMID: 20048159Free PMC Article
Hermos CR, Huizing M, Kaiser-Kupfer MI, Gahl WA
Hum Mutat 2002 Dec;20(6):482. doi: 10.1002/humu.9097. PMID: 12442288
Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B
Mol Genet Metab 2002 Jul;76(3):234-42. PMID: 12126938
Gahl WA, Brantly M, Kaiser-Kupfer MI, Iwata F, Hazelwood S, Shotelersuk V, Duffy LF, Kuehl EM, Troendle J, Bernardini I
N Engl J Med 1998 Apr 30;338(18):1258-64. doi: 10.1056/NEJM199804303381803. PMID: 9562579

Clinical prediction guides

Yang Q, He X, Yang L, Zhou Z, Cullinane AR, Wei A, Zhang Z, Hao Z, Zhang A, He M, Feng Y, Gao X, Gahl WA, Huizing M, Li W
Traffic 2012 Aug;13(8):1160-9. Epub 2012 May 28 doi: 10.1111/j.1600-0854.2012.01375.x. PMID: 22554196Free PMC Article
Kloer DP, Rojas R, Ivan V, Moriyama K, van Vlijmen T, Murthy N, Ghirlando R, van der Sluijs P, Hurley JH, Bonifacino JS
J Biol Chem 2010 Mar 5;285(10):7794-804. Epub 2010 Jan 4 doi: 10.1074/jbc.M109.069088. PMID: 20048159Free PMC Article
Hazzan D, Seward S, Stock H, Zisman S, Gabriel K, Harpaz N, Bauer JJ
Colorectal Dis 2006 Sep;8(7):539-43. doi: 10.1111/j.1463-1318.2006.01046.x. PMID: 16919103
Hussain N, Quezado M, Huizing M, Geho D, White JG, Gahl W, Mannon P
Clin Gastroenterol Hepatol 2006 Jan;4(1):73-80. PMID: 16431308
Gahl WA, Brantly M, Troendle J, Avila NA, Padua A, Montalvo C, Cardona H, Calis KA, Gochuico B
Mol Genet Metab 2002 Jul;76(3):234-42. PMID: 12126938

Supplemental Content

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...
Support Center