Hermansky-Pudlak syndrome

ヘルマンスキー・パドラック症候群

WordNet

1. a pattern of symptoms indicative of some disease
2. a complex of concurrent things; "every word has a syndrome of meanings"

PrepTutorEJDIC

1. (疾患の徴候となる一群の)症徴候,症候群 / (事件・社会的状態などのパターンを示す)徴候形態

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/10/16 17:44:58」(JST)

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Hermansky–Pudlak syndrome
Classification and external resources
Specialty	endocrinology
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 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. 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. A ninth type has also been described. This last type is due to a mutation in the gene Pallidin (PLDN).

Prognosis

The course of HPS has been mild in rare instances of the disorder, 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. This is a fatal complication seen in many forms of HPS, and is the usual cause of death from the disorder. HPS patients who develop pulmonary fibrosis typically have type 1 or type 4.

Diagnosis

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.

Causes

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.

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.

Symptoms

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.
• Is associated with Granulomatous Colitis.

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

Treatment

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

Considerations for patients

A preoperative pulmonology 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.

Eponym

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

See also

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

References

External links

• GeneReviews/NCBI/NIH/UW entry on Hermansky-Pudlak Syndrome
• Hermansky–Pudlak Syndrome Network
• NOAH/albinism.org information about HPS

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

• 1. 先天性および後天性血小板機能障害 congenital and acquired disorders of platelet function
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English Journal

• A divalent interaction between HPS1 and HPS4 is required for the formation of the Biogenesis of Lysosome-related Organelle Complex -3 (BLOC-3).

• Carmona-Rivera C, Simeonov DR, Cardillo ND, Gahl WA, Cadilla CL.SourceUniversity of Puerto Rico, School of Medicine, Department of Biochemistry, P.O. Box 365067, San Juan, PR 00936-5067; Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892.
• Biochimica et biophysica acta.Biochim Biophys Acta.2012 Oct 23. pii: S0167-4889(12)00301-1. doi: 10.1016/j.bbamcr.2012.10.019. [Epub ahead of print]
• Hermansky-Pudlak syndrome (HPS) is a group of rare autosomal recessive disorders characterized by oculocutaneous albinism, a bleeding tendency, and sporadic pulmonary fibrosis, granulomatous colitis or infections. Nine HPS-causing genes have been identified in humans. HPS-1 is the most severe subtyp
• PMID 23103514

• BLOC-3 Mutated in Hermansky-Pudlak Syndrome Is a Rab32/38 Guanine Nucleotide Exchange Factor.

• Gerondopoulos A, Langemeyer L, Liang JR, Linford A, Barr FA.SourceDepartment of Biochemistry, University of Oxford, South Parks Road, Oxford OX1 3QU, UK.
• Current biology : CB.Curr Biol.2012 Oct 16. pii: S0960-9822(12)01084-6. doi: 10.1016/j.cub.2012.09.020. [Epub ahead of print]
• Hermansky-Pudlak syndrome (HPS) is a human disease characterized by partial loss of pigmentation and impaired blood clotting [1-3]. These symptoms are caused by defects in the biogenesis of melanosomes and platelet dense granules, often referred to as lysosome-related organelles [2]. Genes mutated i
• PMID 23084991

Japanese Journal

• A Novel Deletion Mutation of Mouse ruby-eye 2 Named ru2[d]/Hps5[ru2-d] Inhibits Melanocyte Differentiation and Its Impaired Differentiation is Rescued by L-tyrosine

• Hirobe Tomohisa,Yoshihara Chihiro,Takeuchi Sakae [他]
• Zoological science 28(11), 790-801, 2011-11
• NAID 40019070942

• 血小板の微細構造 (特集 血小板--核のない"細胞")

• 鈴木 英紀
• 細胞 43(2), 51-55, 2011-02
• NAID 40018744095

Related Links

• Hermansky-Pudlak症候群

Hermansky-Pudlak症候群（HPS）は，1959. 年，眼・皮膚色素脱出症（oculocutaneous al - binism）に，血小板機能的低下に基づく出血傾 ..... Pudlak症候群における間質性 肺炎の検討.日本胸部疾患. 229. 半田 誠 :Hermansky-Pudlak症候群 ...

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「ヘルマンスキー・パドラック症候群」

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英

Hermansky-Pudlak syndrome

同

ヘルマンスキー・プドラック症候群、Hermansky-Pudlak症候群、ヘルマンスキー・プドゥラック症候群

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血小板機能異常症

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ヘルマンスキー Hermansky : 82 件
ハーマンスキー Hermansky : 21 件

ヘルマンスキー・プドラック症候群 : 54 件
ヘルマンスキー・パドラック症候群 : 59 件

参考

• HERMANSKY-PUDLAK SYNDROME

http://www.ncbi.nlm.nih.gov/omim/203300

http://hps.inochi.info/

「HPS」

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• 肝肺症候群 hepatopulmonary syndrome
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• ヘルマンスキー・プドラック症候群 Hermansky-Pudlak syndrome

「ヘルマンスキー・プドラック症候群」

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英

Hermansky-Pudlak syndrome、HPS

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出血型白皮症候群 albinism-hemorrhagic diathesis syndrome

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Hermansky-Pudlak症候群、ヘルマンスキー・パドラック症候群

「Hermanski-Pudlak syndrome」

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;関:Hermansky-Pudlak syndrome

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Hermansky-Pudlak syndrome

• Hermansky-Pudlak syndrome

「syndrome」

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• 症候群