sphingolipidoses

スフィンゴリピドーシス

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/02/20 21:48:15」(JST)

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Sphingolipidoses
Classification and external resources
Diagram showing some of the sphingolipidoses
ICD-10	E75.3
ICD-9	272.7
DiseasesDB	33438
MeSH	D013106

Sphingolipidoses are a class of lipid storage disorders relating to sphingolipid metabolism. The main members of this group are Niemann-Pick disease, Fabry disease, Krabbe disease, Gaucher disease, Tay-Sachs disease and Metachromatic leukodystrophy. They are generally inherited in an autosomal recessive fashion, but notably Fabry disease is X-linked recessive. Taken together, sphingolipidoses have an incidence of approximately 1 in 10,000, but substantially more in certain populations such as Ashkenazi Jews. Enzyme replacement therapy is available to treat mainly Fabry disease and Gaucher disease, and people with these types of sphingolipidoses may live well into adulthood. The other types are generally fatal by age 1 to 5 years for infantile forms, but progression may be mild for juvenile- or adult-onset forms.

Accumulated products

• Gangliosides: Gangliosidosis
  • GM1 gangliosidoses
  • GM2 gangliosidoses
    • Tay-Sachs disease
    • Sandhoff disease
• Glycolipids
  • Fabry's disease
  • Krabbe disease
  • Metachromatic leukodystrophy
• Glucocerebrosides
  • Gaucher's disease

Overview

Table

Comparison of the main sphingolipidoses

Disease	Deficient enzyme	Accumulated products	Symptoms	Inheritance	Incidence	Generally accepted treatments	Prognosis
Niemann-Pick disease	Sphingomyelinase	Sphingomyelin in brain and RBCs	Mental retardation Spasticity Seizures Hepatosplenomegaly Thrombocytopenia Ataxia	Autosomal recessive	1 in 100,000	Limited	Usually fatal by the age of approx 1.5 years.
Fabry disease	α-galactosidase A	Glycolipids, particularly ceramide trihexoside, in brain, heart, kidney	Ischemic infarction in affected organs Acroparesthesia Angiokeratomas hypohidrosis	X-linked	Between 1 in 40,000 to 1 in 120,000 live births for males.	Enzyme replacement therapy (but expensive)	Life expectancy among males of approximately 60 years.
Krabbe disease	Galactocerebrosidase	Glycolipids, particularly galactocerebroside, in oligodendrocytes	Spasticity Neurodenegeration (leading to death) Hypertonia Hyperreflexia Decerebration-like posture Blindness Deafness	Autosomal recessive	About 1 in 100,000 births.	Limited	Generally fatal before age 2 for infants
Gaucher disease	Glucocerebrosidase	Glucocerebrosides in RBCs, liver and spleen	Hepatosplenomegaly Pancytopenia Bone pain Erlenmeyer flask deformity	Autosomal recessive	About 1 in 20,000 live births, more among Ashkenazi Jews	Enzyme replacement therapy (but expensive)	May live well into adulthood
Tay-Sachs disease	Hexosaminidase A	GM2 gangliosides in neurons	Neurodegeneration Developmental disability Early death	Autosomal recessive	Approximately 1 in 320,000 newborns in the general population, more in Ashkenazi Jews	None	Death by approx. 4 years for infantile Tay–Sachs
Metachromatic leukodystrophy (MLD)	Arylsulfatase A or prosaposin	Sulfatide compounds in neural tissue	Demyelinisation in CNS and PNS: Mental retardation Motor dysfunction Ataxia Hyporeflexia Seizures	Autosomal recessive	1 in 40,000 to 1 in 160,000	None	Death by approx. 5 years for infantile MLD

Metabolic pathways

See also

• Lipid storage disorder

References

External links

• Sphingolipidoses at the US National Library of Medicine Medical Subject Headings (MeSH)
• -382402491 at GPnotebook

UpToDate Contents

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• 1. 先天性代謝異常：分類 inborn errors of metabolism classification
• 2. ムコ多糖症の臨床的特徴および診断 clinical features and diagnosis of the mucopolysaccharidoses

English Journal

• From sheep to mice to cells: Tools for the study of the sphingolipidoses.

• Zigdon H1, Meshcheriakova A1, Futerman AH2.
• Biochimica et biophysica acta.Biochim Biophys Acta.2014 Aug;1841(8):1189-1199. doi: 10.1016/j.bbalip.2014.02.008. Epub 2014 Mar 4.
• The sphingolipidoses are a group of inherited lysosomal storage diseases in which sphingolipids accumulate due to the defective activity of one or other enzymes involved in their degradation. For most of the sphingolipidoses, little is known about the molecular mechanisms that lead to disease, which
• PMID 24607565

• Lysosomal multienzyme complex: pros and cons of working together.

• Bonten EJ1, Annunziata I, d'Azzo A.
• Cellular and molecular life sciences : CMLS.Cell Mol Life Sci.2014 Jun;71(11):2017-32. doi: 10.1007/s00018-013-1538-3. Epub 2013 Dec 15.
• The ubiquitous distribution of lysosomes and their heterogeneous protein composition reflects the versatility of these organelles in maintaining cell homeostasis and their importance in tissue differentiation and remodeling. In lysosomes, the degradation of complex, macromolecular substrates require
• PMID 24337808

• Reflections on 50 years of newborn screening.

• Boyle CA1, Bocchini JA Jr2, Kelly J3.
• Pediatrics.Pediatrics.2014 Jun;133(6):961-3. doi: 10.1542/peds.2013-3658. Epub 2014 May 19.
• PMID 24843062

Japanese Journal

• My journey into the world of sphingolipids and sphingolipidoses

• SANDHOFF Konrad
• Proceedings of the Japan Academy, Series B 88(10), 554-582, 2012
• … Biosynthesis and intracellular trafficking of lysosomal hydrolases (hexosaminidases, acid sphingomyelinase and ceramidase) and lipid binding and transfer proteins (GM2 activator, saposins) were analyzed to identify the molecular and metabolic basis of several sphingolipidoses. …
• NAID 130002540350

• Kunihiko Suzuki and sphingolipidoses

• Ohno Kousaku
• The journal of biochemistry 150(6), 597-605, 2011-12-01
• NAID 10030588962

• Normal phase liquid chromatography coupled to quadrupole time of flight atmospheric pressure chemical ionization mass spectrometry for separation, detection and mass spectrometric profiling of neutral sphingolipids and cholesterol

• FARWANAH Hany,WIRTZ Jennifer,KOLTER Thomas,RAITH Klaus,NEUBERT Reinhard H. H.,SANDHOFF Konrad
• Journal of chromatography. B, Analytical technologies in the biomedical and life sciences 877(27), 2976-2982, 2009-10-01
• NAID 10028024702

Related Links

• Sphingolipidoses - National Center for Biotechnology Information

Brady RO. The sphingolipidoses. N Engl J Med. 1966 Aug 11; 275 (6):312–318. [PubMed] CROCKER AC, FARBER S. Niemann-Pick disease: a review of eighteen patients. Medicine (Baltimore) 1958 Feb; 37 (1):1–95. [PubMed] ...

• Sphingolipidoses - MEDICAL DIAGNOSIS AND MEDICINAL ...

Sphingolipidoses. On-line free medical diagnosis assistant. Ranked list of possible diseases from either several symptoms or a full patient history. A similarity measure between symptoms and diseases is provided. ... A group of ...

Related Pictures

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★リンクテーブル★

リンク元	「スフィンゴリピドーシス」「常染色体劣性遺伝病」

「スフィンゴリピドーシス」

　　[★]

英

sphingolipidoses

同

スフィンゴリピド症

関

スフィンゴリポジストロフィー

• GM2-ガングリオシドーシス

• βヘキソサミニダーゼα鎖欠損症
• βヘキソサミニダーゼβ鎖欠損症 Sandhoff病
• 活性化蛋白欠損症

• GM1-ガングリオシドーシス
• Niemann-Pick病
• Gaucher病
• Fabry病
• Krabbe病

Disease	Enzyme Deficiency	Lipid Accumulating	Clinical Symptoms
Tay-Sachs disease	Hexosaminidase A	Cer-Glc-Gal(NeuAc)-: : GalNAc GM2 Ganglioside	Mental retardation, blindness, muscular weakness.
Fabry's disease	α-Galactosidase	Cer-Glc-Gal-: : Gal Globotriaosylceramide	Skin rash, kidney failure (full symptoms only in males; X-linked recessive).
Metachromatic leukodystrophy	Arylsulfatase A	Cer-Gal-: : OSO3 3-Sulfogalactosylceramide	Mental retardation and psychologic disturbances in adults; demyelination.
Krabbe's disease	β-Galactosidase	Cer-: : Gal Galactosylceramide	Mental retardation; myelin almost absent.
Gaucher's disease	β-Glucosidase	Cer-: : Glc Glucosylceramide	Enlarged liver and spleen, erosion of long bones, mental retardation in infants.
Niemann-Pick disease	Sphingomyelinase	Cer-: : P-choline Sphingomyelin	Enlarged liver and spleen, mental retardation; fatal in early life.
Farber's disease	Ceramidase	Acyl-: : Sphingosine Ceramide	Hoarseness, dermatitis, skeletal deformation, mental retardation; fatal in early life.

「常染色体劣性遺伝病」

　　[★]

英

autosomal recessive disease, autosomal recessive disorder

同

常染色体劣性遺伝疾患

関

遺伝病、常染色体優性遺伝病

autosomal-recessive diseases(first aid step　1 p.108)

• 嚢胞線維症 cystic fibrosis
• 白皮症 albinism
• α1アンチトリプシン欠損症 α1-antitrypsin deficiency
• フェニルケトン尿症 phenylketonuria
• サラセミア thalassemias
• 鎌状赤血球貧血 sickle cell anemia
• グリコーゲン貯蔵病 glycogen storage disease
• ムコ多糖症(ハンター症候群以外) mucopolysaccharidoses (except Hunter's syndrome)
• スフィンゴリピドーシス(ファブリー病以外) sphingolipidoses (except Fabry's disease)
• 幼児型嚢胞腎 infant polycystic kidney disease
• ヘモクロマトーシス hemochromatosis