Hermansky–Pudlak syndrome

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Hermansky–Pudlak syndrome
Classification and external resources
ICD-10 E70.3
(ILDS E70.360)
OMIM 203300
DiseasesDB 29161
eMedicine oph/713 derm/925
MeSH D022861

Hermansky–Pudlak syndrome (HPS) is a rare autosomal recessive[1] disorder which results in oculocutaneous albinism (decreased pigmentation), bleeding problems due to a platelet abnormality (platelet storage pool defect), and storage of an abnormal fat-protein compound (lysosomal accumulation of ceroid lipofuscin).

It is considered to affect around 1 in 500,000 people worldwide, with a significantly higher occurrence in Puerto Ricans, with a prevalence of 1 in 1800.[2] Many of the clinical research studies on the disease have been conducted in Puerto Rico.

There are eight classic forms of the disorder, based on the genetic mutation from which the disorder stems.[3] A ninth type has also been described.[4] This last type is due to a mutation in the gene Pallidin (PLDN).

Prognosis[edit]

The course of HPS has been mild in rare instances of the disorder,[5] however, the general prognosis is still considered to be poor.

The disease can cause dysfunctions of the lungs, intestine, kidneys or heart. The major complication of most forms of the disorder is pulmonary fibrosis, which typically exhibits in patients ages 40–50 years.[6] This is a fatal complication seen in many forms of HPS, and is the usual cause of death from the disorder.[7] HPS patients who develop pulmonary fibrosis typically have type 1 or type 4.

Diagnosis[edit]

The diagnosis of HPS is established by clinical findings of hypopigmentation of the skin and hair, characteristic eye findings, and demonstration of absent dense bodies on whole mount electron microscopy of platelets. Molecular genetic testing of the HPS1 gene is available on a clinical basis for individuals from northwestern Puerto Rico. Molecular testing of the HPS3 gene is available on a clinical basis for individuals of central Puerto Rican or Ashkenazi Jewish heritage. Sequence analysis is available on a clinical basis for mutations in HPS1 and HPS4. Diagnosis of individuals with other types of HPS is available on a research basis only.[8]

Causes[edit]

HPS can be caused by mutations in several genes: HPS1, HPS3, HPS4, HPS5, HPS6 and HPS7.

HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in the AP3B1 gene.

HPS type 7 may result from a mutation in the gene coding for dysbindin protein.[9]

Hermansky–Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP, responsible for this disorder is located on the long arm of chromosome 10 (10q2). Some research suggests that an abnormality of lysosomal function may be responsible for the development of the disease. HPS1, AP3B1, HPS3, HPS4, HPS5, HPS6, DTNBP1 and BLOC1S3 are associated with Hermansky–Pudlak syndrome.

In autosomal recessive disorders, the condition does not appear unless a person inherits two copies of the defective gene responsible for the disorder, one copy coming from each parent. If an individual receives one normal gene and one gene for the disorder, the person will be a carrier for the disease, but usually will not show symptoms. The risk of transmitting the disease to the children of a couple, both of whom are carriers for a recessive disorder, is 25 percent. Fifty percent of their children risk being carriers of the disease, but generally will not show symptoms of the disorder. Twenty-five percent of their children may receive both normal genes, one from each parent, and will be genetically normal (for that particular trait). The risk is the same for each pregnancy.[10]

Symptoms[edit]

There are three main disorders caused by Hermansky–Pudlak syndrome, which result in these symptoms:

  • Albinism and eye problems: Individuals will have varying amounts of skin pigment (melanin). Because of the albinism there are eye problems such as light sensitivity (photophobia), strabismus (crossed eyes), and nystagmus (involuntary eye movements). Hermansky–Pudlak syndrome also impairs vision.
  • Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.
  • Cellular storage disorders: The syndrome causes a wax-like substance (ceroid) to accumulate in the body tissues and cause damage, especially in the lungs and kidneys.[11]
  • Is associated with Granulomatous Colitis.

It also associated with Pulmonary Fibrosis, a fatal lung disease.

Treatment[edit]

While there is no cure for HPS, treatment for chronic hemorrhages associated with the disorder includes therapy with vitamin E and the antidiuretic dDAVP.[12]

Considerations for patients[edit]

A preoperative pneumologist consultation is needed. The anesthesia team should be aware that patients may have postoperative pulmonary complications as part of the syndrome.

Preoperative hematology consultation is advisable prior to elective ocular surgeries. Since patients with the syndrome have bleeding tendencies, intraoperative, perioperative, and postoperative hemorrhages should be prevented and treated. If platelet aggregation improves with desmopressin, it may be administered in the preoperative period. However, sometimes plasmapheresis is needed in the perioperative period.

Ophthalmologists should try to avoid retrobulbar blocks in patients with the syndrome. Whenever possible, patients with HPS may benefit from general endotracheal anesthesia. Phacoemulsification may help prevent intraoperative and postoperative bleeding in patients with the syndrome. Prolonged bleeding has been reported following strabismus surgery in patients with the syndrome. [13]

Eponym[edit]

It is named for Frantisek Hermansky (1916–1980) and Paulus Pudlak (1921–1984).[14][15]

See also[edit]

References[edit]

  1. ^ Oh, J; Ho, L; Ala-Mello, S; Amato, D; Armstrong, L; Bellucci, S; Carakushansky, G; Ellis, Jp; Fong, Ct; Green, Js; Heon, E; Legius, E; Levin, Av; Nieuwenhuis, Hk; Pinckers, A; Tamura, N; Whiteford, Ml; Yamasaki, H; Spritz, Ra (March 1998). "Mutation analysis of patients with Hermansky–Pudlak syndrome: a frameshift hot spot in the HPS gene and apparent locus heterogeneity". American Journal of Human Genetics 62 (3): 593–8. doi:10.1086/301757. PMC 1376951. PMID 9497254. 
  2. ^ Santiago Borrero PJ, Rodríguez-Pérez Y, Renta JY, et al. (January 2006). "Genetic testing for oculocutaneous albinism type 1 and 2 and Hermansky–Pudlak syndrome type 1 and 3 mutations in Puerto Rico". J. Invest. Dermatol. 126 (1): 85–90. doi:10.1038/sj.jid.5700034. PMID 16417222. 
  3. ^ Online 'Mendelian Inheritance in Man' (OMIM) 203300
  4. ^ Cullinane AR, Curry JA, Carmona-Rivera C, Summers CG, Ciccone C, Cardillo ND, Dorward H, Hess RA, White JG et al. (2011). "A BLOC-1 Mutation Screen Reveals that PLDN Is Mutated in Hermansky-Pudlak Syndrome Type 9". Am J Hum Genet 88 (6): 778–787. doi:10.1016/j.ajhg.2011.05.009. 
  5. ^ Schallreuter, Ku; Frenk, E; Wolfe, Ls; Witkop, Cj; Wood, Jm (1993). "Hermansky–Pudlak syndrome in a Swiss population" (Free full text). Dermatology (Basel, Switzerland) 187 (4): 248–56. doi:10.1159/000247258. ISSN 1018-8665. PMID 8274781. 
  6. ^ Depinho, Ra; Kaplan, Kl (May 1985). "The Hermansky–Pudlak syndrome. Report of three cases and review of pathophysiology and management considerations". Medicine 64 (3): 192–202. doi:10.1097/00005792-198505000-00004. ISSN 0025-7974. PMID 3921802. 
  7. ^ Davies, Bh; Tuddenham, Eg (April 1976). "Familial pulmonary fibrosis associated with oculocutaneous albinism and platelet function defect. A new syndrome". The Quarterly journal of medicine 45 (178): 219–32. ISSN 0033-5622. PMID 940919. 
  8. ^ "Hermansky–Pudlak Syndrome". Retrieved 2008-11-24. 
  9. ^ Li W, Zhang Q, Oiso N, Novak EK, Gautam R, O'Brien EP, Tinsley CL, Blake DJ, Spritz RA, Copeland NG, Jenkins NA, Amato D, Roe BA, Starcevic M, Dell'Angelica EC, Elliott RW, Mishra V, Kingsmore SF, Paylor RE, Swank RT (2003). "Hermansky–Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1)". Nat. Genet. 35 (1): 84–9. doi:10.1038/ng1229. PMC 2860733. PMID 12923531. 
  10. ^ "CIGNA - Hermansky–Pudlak Syndrome". Retrieved 2008-11-24. 
  11. ^ "Hermansky–Pudlak Syndrome". Retrieved 2008-11-24. 
  12. ^ Wijermans, Pw; Van, Dorp, Db (March 1989). "Hermansky–Pudlak syndrome: correction of bleeding time by 1-desamino-8D-arginine vasopressin". American journal of hematology 30 (3): 154–7. doi:10.1002/ajh.2830300307. ISSN 0361-8609. PMID 2916560. 
  13. ^ "Hermansky–Pudlak Syndrome". Retrieved 2008-11-24. 
  14. ^ synd/2220 at Who Named It?
  15. ^ Hermansky, F; Pudlak, P (1 February 1959). "Albinism associated with hemorrhagic diathesis and unusual pigmented reticular cells in the bone marrow: report of two cases with histochemical studies." (Free full text). Blood 14 (2): 162–9. ISSN 0006-4971. PMID 13618373. 

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