gargoylism

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/10/27 21:32:54」(JST)

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Hurler syndrome
Classification and external resources
ICD-10	E76.0
ICD-9	277.5
OMIM	607014
DiseasesDB	6067
MedlinePlus	001204
eMedicine	ped/1031
MeSH	D008059
GeneReviews	Mucopolysaccharidosis Type I

Hurler syndrome, also known as mucopolysaccharidosis type I (MPS I), Hurler's disease, also gargoylism, is a genetic disorder that results in the buildup of glycosaminoglycans (formerly known as mucopolysaccharides) due to a deficiency of alpha-L iduronidase, an enzyme responsible for the degradation of mucopolysaccharides in lysosomes. Without this enzyme, a buildup of heparan sulfate and dermatan sulfate occurs in the body. Symptoms appear during childhood and early death can occur due to organ damage.

MPS I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme α-L-iduronidase. MPS I H or Hurler syndrome is the most severe of the MPS I subtypes. The other two types are MPS I S or Scheie syndrome and MPS I H-S or Hurler-Scheie syndrome.

Hurler syndrome is often classified as a lysosomal storage disease, and is clinically related to Hunter Syndrome. Hunter syndrome is X-linked while Hurler syndrome is autosomal recessive.

It is named for Gertrud Hurler (1889–1965), a German pediatrician.

Prevalence

Hurler syndrome has an overall frequency of 1 per 100,000. The mucopolysaccharidoses as a whole have a frequency of 1 in every 25,000 births.^{[citation needed]}

Genetics

Hurler syndrome has an autosomal recessive pattern of inheritance.

Children born to an MPS I parent carry a defective IDUA gene, which has been mapped to the 4p16.3 site on chromosome 4. The gene is named IDUA because of its iduronidase enzyme protein product. As of 2001, 52 different mutations in the IDUA gene have been shown to cause Hurler syndrome.

Because Hurler syndrome is an autosomal recessive disorder, affected persons have two non-working copies of the IDUA gene. If someone is born with one normal and one defective copy of the gene (s)he is called a carrier and will produce less α-L-iduronidase than an individual with two normal copies of the gene. The slightly reduced production of the enzyme in carriers, however, remains sufficient for normal function and the person should not show any symptoms of the disease.

Features

The condition is marked by progressive deterioration, hepatosplenomegaly, dwarfism and unique facial features. There is a progressive mental retardation, with death frequently occurring by the age of 10 years.

Developmental delay is evident by the end of the first year, and patients usually stop developing between ages 2 and 4. This is followed by progressive mental decline and loss of physical skills. Language may be limited due to hearing loss and an enlarged tongue. In time, the clear layers of the cornea become clouded and retinas may begin to degenerate. Carpal tunnel syndrome (or similar compression of nerves elsewhere in the body) and restricted joint movement are common.

Affected children may be large at birth and appear normal but may have inguinal (in the groin) or umbilical (where the umbilical cord passes through the abdomen) hernias. Growth in height may be initially faster than normal, then begins to slow before the end of the first year and often ends around age 3. Many children develop a short body trunk and a maximum stature of less than 4 feet. Distinct facial features (including flat face, depressed nasal bridge, and bulging forehead) become more evident in the second year. By age 2, the ribs have widened and are oar-shaped. The liver, spleen and heart are often enlarged. Children may experience noisy breathing and recurring upper respiratory tract and ear infections. Feeding may be difficult for some children, and many experience periodic bowel problems. Children with Hurler syndrome often die before age 10 from obstructive airway disease, respiratory infections, or cardiac complications.

Diagnosis

Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the mucopolysaccharidoses. Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders.

Treatment

Enzyme replacement therapies are currently in use, BioMarin Pharmaceutical provides therapeutics for mucopolysaccaradosis type I (MPS I), by manufacturing laronidase (Aldurazyme), commercialized by Genzyme. Enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain.

Bone marrow transplantation (BMT) and umbilical cord blood transplantation (UCBT) can be used as treatments for MPS. Abnormal physical characteristics, except for those affecting the skeleton and eyes, can be improved, and neurologic degeneration can often be halted. BMT and UCBT are high-risk procedures with high rates of morbidity and mortality. There is no cure for MPS I.

Gene Therapy

There is currently a great deal of interest in treating MPS I with gene therapy. This approach has been taken with retroviral, lentiviral, AAV, and even nonviral vectors to deliver the iduronidase gene. Successful treatment of the mouse, dog, and cat models of MPS I has occurred and may pave the way to human trials in the future.

See also

• Hunter syndrome

References

External links

• National MPS Society
• GeneReview/NIH/UW entry on Mucopolysaccharidosis Type I
• Hurler Syndrome Community

English Journal

• Postnatal progression of bone disease in the cervical spines of mucopolysaccharidosis I dogs.

• Chiaro JA, Baron MD, Del Alcazar CM, O'Donnell P, Shore EM, Elliott DM, Ponder KP, Haskins ME, Smith LJ.SourceDepartment of Orthopaedic Surgery, Perelman School of Medicine, University of Pennsylvania, 424 Stemmler Hall, 3450 Hamilton Walk, Philadelphia, PA 19104, USA.
• Bone.Bone.2013 Jul;55(1):78-83. doi: 10.1016/j.bone.2013.03.014. Epub 2013 Apr 4.
• INTRODUCTION: Mucopolysaccharidosis I (MPS I) is a lysosomal storage disorder characterized by deficient α-l-iduronidase activity leading to accumulation of poorly degraded dermatan and heparan sulfate glycosaminoglycans (GAGs). MPS I is associated with significant cervical spine disease, including
• PMID 23563357

• Does early use of enzyme replacement therapy alter the natural history of mucopolysaccharidosis I? Experience in three siblings.

• Laraway S, Breen C, Mercer J, Jones S, Wraith JE.SourceGenetic Medicine, Manchester Academic Health Science Centre, University of Manchester, Central Manchester University Hospitals NHS Foundation Trust, St. Mary's Hospital, Oxford Road, Manchester M13 9WL, UK.
• Molecular genetics and metabolism.Mol Genet Metab.2013 Jul;109(3):315-6. doi: 10.1016/j.ymgme.2013.04.023. Epub 2013 May 10.
• Enzyme replacement therapy is widely used as treatment for mucopolysaccharidosis I (MPS I), and there is evidence that this produces improvement in certain clinical domains. There does appear to be variation in the response of clinical features to treatment once these are established. In a reported
• PMID 23721889

Japanese Journal

• An Adult Case with Hunters Syndrome Presenting Prominent Hepatic Failure: Light and Electron Microscopic Features of the Liver

• Yoshimoto Tsuyoshi,Nakamuta Makoto,Kotoh Kazuhiro,Kohjima Motoyuki,Morizono Shusuke,Miyagi Yuzuru,Sakai Hironori,Enjoji Munechika
• Internal Medicine 45(20), 1133-1135, 2006
• We describe a 40-year-old male patient with Hunters syndrome. His main manifestations were ascites and esophageal varices due to cirrhotic liver. We obtained hepatic biopsy samples and examined them. …
• NAID 130000076627

• A Case of Gargoylism

• 迫田 安征,木山 吉正,楊 国雄,日高 恒彦,平部 久彬
• 整形外科と災害外科 24(2), 166-169, 1975
• Gagroylism, congenital disorder of mucopolysaccharide metabolism, was first described by Hunter in 1917. Its main clinical features are as follows; 1) mental retardation, 2) dwarfism, 3) Gargoyle appe …
• NAID 130001637336

• 高年者にみるHurler症候群(Gargoylism)とその剖検所見

• 王丸 勇 [他]
• 久留米医学会雑誌 37(4), 211-224, 1974-04
• NAID 40017691720

Related Links

• gargoylism - definition of gargoylism by Medical dictionary

gargoylism /gar·goyl·ism/ (gahr´goil-izm) Hurler's syndrome. gar·goyl·ism (gär goil z m) n. A condition characterized by coarsened facial surface and distorted features and associated with Hurler's syndrome and Hunter's syndrome.

• Gargoylism | Define Gargoylism at Dictionary.com

Gargoylism definition, a congenital abnormality characterized chiefly by dwarfism, grotesque deformities of the head, trunk, and limbs, mental retardation, and enlargement of the liver and spleen. See more. Thesaurus Translator ...

• Gargoylism - RightDiagnosis.com - Right Diagnosis

Gargoylism symptoms, causes, diagnosis, and treatment information for Gargoylism (Mucopolysaccharidosis type I Hurler syndrome) with alternative diagnoses, full-text book chapters, misdiagnosis, research treatments, prevention ...

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リンク元	「ハーラー症候群」「ガーゴイリスム」

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英

Hurler's syndrome, Hurler syndrome

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(症候群)Hurler症候群、ガーゴイリスム gargoylism, Gargoylismus、ムコ多糖症IH, mucopolysaccharidosis IH, MPS IH、ファンドラー・ハーラー病 Pfaundler-Hurler disease

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ハーラー・シャイエ症候群、ムコ多糖症、ムコ多糖症I型

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英

gargoylism

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ハーラー症候群