Hermansky–Pudlak syndrome

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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.{{citation needed|date=February 2016}}
• Bleeding disorders: Individuals with the syndrome have platelet dysfunction. Since platelets are necessary for blood clotting, individuals will bruise and bleed easily.{{citation needed|date=February 2016}}
• 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.{{cite web |url=http://rarediseases.about.com/od/rarediseasesh/a/090404.htm |title=Hermansky–Pudlak Syndrome |access-date=24 November 2008 |archive-date=21 September 2015 |archive-url=https://web.archive.org/web/20150921195201/http://rarediseases.about.com/od/rarediseasesh/a/090404.htm |url-status=dead}}

It is also associated with granulomatous colitis,{{citation needed|date=February 2016}}, an inflammation of the colon, and with pulmonary fibrosis,{{citation needed|date=October 2017}} a potentially fatal lung disease.

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HPS can be caused by mutations in several genes: HPS1, HPS3, HPS4, HPS5, HPS6 and HPS7.{{citation needed|date=February 2016}}

HPS type 2, which includes immunodeficiency in its phenotype, is caused by mutation in the AP3B1 gene.{{citation needed|date=February 2016}}

HPS type 7 may result from a mutation in the gene coding for dysbindin protein.{{cite journal |last1=Li |first1=W. |last2=Zhang |first2=Q. |last3=Oiso |first3=N. |last4=Novak |first4=E. K. |last5=Gautam |first5=R. |last6=O'Brien |first6=E. P. |last7=Tinsley |first7=C. L. |last8=Blake |first8=D. J. |last9=Spritz |first9=R. A. |last10=Copeland |first10=N. G. |last11=Jenkins |first11=N. A. |last12=Amato |first12=D. |last13=Roe |first13=B. A. |last14=Starcevic |first14=M. |last15=Dell'Angelica |first15=E. C. |last16=Elliott |first16=R. W. |last17=Mishra |first17=V. |last18=Kingsmore |first18=S. F. |last19=Paylor |first19=R. E. |last20=Swank |first20=R. T. |title=Hermansky–Pudlak syndrome type 7 (HPS-7) results from mutant dysbindin, a member of the biogenesis of lysosome-related organelles complex 1 (BLOC-1) |journal=Nature Genetics |volume=35 |issue=1 |pages=84–89 |date=2003 |pmid=12923531 |doi=10.1038/ng1229 |pmc=2860733}}

Hermansky–Pudlak syndrome is thought to be inherited as an autosomal recessive genetic trait. The defective gene, called HSP {{dubious|HPS1 and HPS6 are located in 10q|date=January 2016}}, 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 Biogenesis of Lysosome-related Organelles Complex (BLOC1, BLOC1S2 and BLOC3) are associated with Hermansky–Pudlak syndrome.{{citation needed|date=February 2016}}

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.{{cite web |url=http://www.cigna.com/healthinfo/nord946.html |work=CIGNA.com |title=Hermansky–Pudlak Syndrome |access-date=14 November 2008}}

The mechanism of Hermansky–Pudlak syndrome indicates that platelets in affected individuals accumulate abnormally with thrombin, epinephrine, and adenosine diphosphate, furthermore platelets in these individuals have a lower amount of dense bodies{{Cite journal |title=Hermansky-Pudlak Syndrome: Background, Pathophysiology, Epidemiology |journal=Medscape |url= http://emedicine.medscape.com/article/1200277-overview#a5 |date=13 June 2017}}

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.{{Cite book |url= https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hps |title=Hermansky–Pudlak Syndrome |access-date=24 November 2008 |publisher=University of Washington, Seattle |date=1993 |pmid=20301464 |last1=Adam |first1=M. P. |last2=Mirzaa |first2=G. M. |last3=Pagon |first3=R. A. |last4=Wallace |first4=S. E. |last5=Bean |first5=L. J. H. |last6=Gripp |first6=K. W. |last7=Amemiya |first7=A. |last8=Introne |first8=W. J. |last9=Huizing |first9=M. |last10=Malicdan |first10=M. C. V. |last11=O'Brien |first11=K. J. |last12=Gahl |first12=W. A.}}

While there is no cure for HPS, treatment for chronic hemorrhages associated with the disorder includes therapy with vitamin E and the antidiuretic dDAVP.{{cite journal |pmid=2916560 |date=March 1989 |last1=Wijermans |first1=P. W. |last2=Van Dorp |first2=D. B. |title=Hermansky–Pudlak syndrome: Correction of bleeding time by 1-desamino-8D-arginine vasopressin |journal=American Journal of Hematology |volume=30 |issue=3 |pages=154–157 |issn=0361-8609 |doi=10.1002/ajh.2830300307|s2cid=43301543}}

A preoperative pulmonology consultation is needed. The anesthesia team should be aware that patients may have postoperative pulmonary complications as part of the syndrome.{{citation needed|date=February 2016}}

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.{{citation needed|date=February 2016}}

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.{{cite web |url=http://www.emedicine.com/oph/topic713.htm |title=Hermansky–Pudlak Syndrome |access-date=24 November 2008}}

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The course of HPS has been mild in rare instances of the disorder,{{cite journal |pmid=8274781 |date=1993 |last1=Schallreuter |first1=Karin U. |author-link1=Karin Schallreuter |last2=Frenk |first2=E. |last3=Wolfe |first3=L. S. |last4=Witkop |first4=C. J. |last5=Wood |first5=J. M. |title=Hermansky–Pudlak syndrome in a Swiss population |journal=Dermatology |volume=187 |issue=4 |pages=248–256 |issn=1018-8665 |url=http://www.geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Vitiligo |archive-url=https://web.archive.org/web/20220123095248/https://geneticalliance.org/ws_display.asp?filter=infosearch_results&info_keyword=Vitiligo |url-status=dead |archive-date=23 January 2022 |doi=10.1159/000247258}} however, the general prognosis is still considered to be poor.{{citation needed|date=February 2016}}The disease can cause dysfunctions of the lungs, intestine, kidneys, and heart. The major complication of most forms of the disorder is pulmonary fibrosis, which typically exhibits in patients ages 40–50 years.{{cite journal |pmid=3921802 |date=May 1985 |last1=Depinho |first1=R. A. |last2=Kaplan |first2=K. L. |s2cid=20833320 |title=The Hermansky–Pudlak syndrome: Report of three cases and review of pathophysiology and management considerations |journal=Medicine |volume=64 |issue=3 |pages=192–202 |issn=0025-7974 |doi=10.1097/00005792-198505000-00004 |doi-access=free}} This is a fatal complication seen in many forms of HPS, and is the usual cause of death from the disorder.{{cite journal |pmid=940919 |date=April 1976 |last1=Davies |first1=B. H. |last2=Tuddenham |first2=E. G. |title=Familial pulmonary fibrosis associated with oculocutaneous albinism and platelet function defect: A new syndrome |journal=The Quarterly Journal of Medicine |volume=45 |issue=178 |pages=219–232 |issn=0033-5622}} HPS patients who develop pulmonary fibrosis typically have type 1 or type 4.{{citation needed|date=February 2016}}

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HPS is one of the rare lung diseases currently being studied by The Rare Lung Diseases Consortium (RLDC). The RLDC is part of the Rare Diseases Clinical Research Network (RDCRN), an initiative of the Office of Rare Diseases Research (ORDR), of the National Center for Advancing Translational Sciences (NCATS). The RLDC is dedicated to developing new diagnostics and therapeutics for patients with rare lung diseases, through collaboration between the NIH, patient organizations and clinical investigators.{{citation needed|date=February 2016}}

• Biogenesis of lysosome-related organelles complex 1
• List of cutaneous conditions

{{Reflist}}

• [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=hps GeneReviews/NCBI/NIH/UW entry on Hermansky-Pudlak Syndrome]

{{Medical resources

| DiseasesDB = 29161

| ICD10 = {{ICD10|E|70|3|e|70}}
(ILDS E70.360)

| ICD9 = {{ICD9|270.2}}

| OMIM = 203300

| MedlinePlus =

| eMedicineSubj = oph

| eMedicineTopic = 713

| eMedicine_mult = {{eMedicine2|derm|925}}

| MeshID = D022861

| GeneReviewsName = Hermansky-Pudlak Syndrome

| GeneReviewsNBK = NBK1287

| Orphanet = 79430

| ICD10CM = {{ICD10CM|E70.331}}

}}

{{Amino acid metabolic pathology}}

{{Diseases of megakaryocytes|us=y}}

{{Pigmentation disorders}}

{{Inherited disorders of trafficking}}

{{DEFAULTSORT:Hermansky-Pudlak Syndrome}}

Category:Disturbances of human pigmentation

Category:Syndromes affecting the skin

Category:Amino acid metabolism disorders

Category:Autosomal recessive disorders

Category:Rare syndromes

Category:Coagulopathies

Category:IUIS-PID table 3 immunodeficiencies

Category:Syndromes affecting blood

Category:Syndromes affecting the lung