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- 〈U〉〈C〉(…の)(量・額などの)不足,欠乏《+『of』(『in』)+『名』》 / 〈C〉不足分,不足量,不足額 / 〈C〉(精神・肉体などの)欠陥
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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/05/22 05:34:30」(JST)
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| Galactokinase deficiency |
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Galactitol
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| Classification and external resources |
| Specialty |
endocrinology |
| ICD-10 |
E74.2 |
| ICD-9-CM |
271.1 |
| OMIM |
230200 |
| DiseasesDB |
29829 |
| eMedicine |
ped/815 |
|
[edit on Wikidata]
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Galactokinase deficiency, also known as Galactosemia type 2 or GALK deficiency,[1] is an autosomal recessive metabolic disorder marked by an accumulation of galactose and galactitol secondary to the decreased conversion of galactose to galactose-1-phosphate by galactokinase.[2] The disorder is caused by mutations in the GALK1 gene, located on chromosome 17q24.[1] Galactokinase catalyzes the first step of galactose phosphorylation in the Leloir pathway of intermediate metabolism. Galactokinase deficiency is one of the three inborn errors of metabolism that lead to hypergalactosemia. The disorder is inherited as an autosomal recessive trait. Unlike classic galactosemia, which is caused by deficiency of galactose-1-phosphate uridyltransferase, galactokinase deficiency does not present with severe manifestations in early infancy. Its major clinical symptom is the development of cataracts during the first weeks or months of life, as a result of the accumulation, in the lens, of galactitol, a product of an alternative route of galactose utilization. The development of early cataracts in homozygous affected infants is fully preventable through early diagnosis and treatment with a galactose-restricted diet. Some studies have suggested that, depending on milk consumption later in life, heterozygous carriers of galactokinase deficiency may be prone to presenile cataracts at 20–50 years of age.[3]
Contents
- 1 Genetics
- 2 Treatment
- 3 See also
- 4 References
Genetics
Galactokinase deficiency has autosomal recessive pattern of inheritance.
Galactokinase deficiency is an autosomal recessive disorder,[4] which means the defective gene responsible for the disorder is located on an autosome (chromosome 17 is an autosome), and two copies of the defective gene (one inherited from each parent) are required in order to be born with the disorder. The parents of an individual with an autosomal recessive disorder both carry one copy of the defective gene, but usually do not experience any signs or symptoms of the disorder.
Unlike galactose-1-phosphate uridyltransferase deficiency, the symptoms of galactokinase deficiency are relatively mild. The only known symptom in affected children is the formation of cataracts, due to production of galactitol in the lens of the eye.[5] Cataracts can present as a failure to develop a social smile and failure to visually track moving objects.
Gene Structure
The human GALK1 gene contains 8 exons and spans approximately 7.3 kb of genomic DNA. The GALK1 promoter was found to have many features in common with other housekeeping genes, including high GC content, several copies of the binding site for the Sp1 transcription factor and the absence of TATA-box and CCAAT-box motifs typically present in eukaryotic polymerase II promoters. Analysis by 5-prime-RACE PCR indicated that the GALK1 mRNA is heterogeneous at the 5-prime end, with transcription sites occurring at many locations between 21 and 61 bp upstream of the ATG start site of the coding region. In vitro translation experiments of the GALK1 cDNA indicated that the protein is cytosolic and not associated with endoplasmic reticulum membrane.[3]
Treatment
Medical Care
- Treatment may be provided on an outpatient basis.
- Cataracts that do not regress or disappear with therapy may require hospitalization for surgical removal.
Surgical Care
- Cataracts may require surgical removal.
Consultations
- Biochemical geneticist
- Nutritionist
- Ophthalmologist
Diet
- Diet is the foundation of therapy. Elimination of lactose and galactose sources suffices for definitive therapy.
Activity
- No restriction is necessary.
(Roth MD, Karl S. 2009)
See also
References
- ^ a b Online 'Mendelian Inheritance in Man' (OMIM) Galactokinase Deficiency -230200
- ^ Holton JB (1990). "Galactose disorders: an overview". J Inherit Metab Dis. 13 (4): 476–486. doi:10.1007/BF01799505. PMID 2122114.
- ^ a b Kalaydjieva L, Perez-Lezaun A, Angelicheva D, et al. (November 1999). "A founder mutation in the GK1 gene is responsible for galactokinase deficiency in Roma (Gypsies)". Am. J. Hum. Genet. 65 (5): 1299–307. doi:10.1086/302611. PMC 1288282. PMID 10521295.
- ^ Asada M, Okano Y, Imamura T, Suyama I, Hase Y, Isshiki G (1999). "Molecular characterization of galactokinase deficiency in Japanese patients". Journal of Human Genetics 44 (6): 377–382. doi:10.1007/s100380050182. PMID 10570908.
- ^ Roth, KS (September 10, 2007). "Galactokinase Deficiency". eMedicine. WebMD. Retrieved 2008-08-08.
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Inborn error of carbohydrate metabolism: monosaccharide metabolism disorders (including glycogen storage diseases) (E73–E74, 271)
|
|
Sucrose, transport
(extracellular) |
| Disaccharide catabolism |
- Congenital alactasia
- Sucrose intolerance
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| Monosaccharide transport |
- Glucose-galactose malabsorption
- Inborn errors of renal tubular transport (Renal glycosuria)
- Fructose malabsorption
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|
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| Hexose → glucose |
| Monosaccharide catabolism |
| fructose: |
- Essential fructosuria
- Fructose intolerance
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| galactose/galactosemia: |
- GALK deficiency
- GALT deficiency/GALE deficiency
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|
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| Glucose ⇄ glycogen |
| Glycogenesis |
- GSD type 0, glycogen synthase
- GSD type IV, Andersen's, branching
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| Glycogenolysis |
| extralysosomal: |
- GSD type V, McArdle, muscle glycogen phosphorylase/GSD type VI, Hers', liver glycogen phosphorylase
- GSD type III, Cori's, debranching
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- lysosomal/LSD: GSD type II, Pompe's, glucosidase
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| Glucose ⇄ CAC |
| Glycolysis |
- MODY 2/HHF3
- GSD type VII, Tarui's, phosphofructokinase
- Triosephosphate isomerase deficiency
- Pyruvate kinase deficiency
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| Gluconeogenesis |
- PCD
- Fructose bisphosphatase deficiency
- GSD type I, von Gierke, glucose 6-phosphatase
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|
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| Pentose phosphate pathway |
- Glucose-6-phosphate dehydrogenase deficiency
- Transaldolase deficiency
- 6-phosphogluconate dehydrogenase deficiency
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| Other |
- Hyperoxaluria
- Pentosuria
- Aldolase A deficiency
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UpToDate Contents
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English Journal
- Detection of common mutations in the GALT gene through ARMS.
- Mahmood U, Imran M, Naik SI, Cheema HA, Saeed A, Arshad M, Mahmood S.SourceDepartment of Biochemistry, University of Health Sciences (UHS), Khayaban-e-Jamia Punjab, Lahore 54600, Pakistan.
- Gene.Gene.2012 Nov 10;509(2):291-4. doi: 10.1016/j.gene.2012.08.010. Epub 2012 Aug 16.
- Type I galactosemia is an inborn error resulting from mutations on both alleles of the GALT gene, which leads to the absence or deficiency of galactose-1-phosphate uridyltranseferase (GALT), the second of three enzymes catalyzing the conversion of galactose into glucose. On the basis of residual GAL
- PMID 22963887
- Altered cofactor binding affects stability and activity of human UDP-galactose 4'-epimerase: implications for type III galactosemia.
- McCorvie TJ, Liu Y, Frazer A, Gleason TJ, Fridovich-Keil JL, Timson DJ.SourceSchool of Biological Sciences, Queen's University, Belfast, BT9 7BL, UK.
- Biochimica et biophysica acta.Biochim Biophys Acta.2012 Oct;1822(10):1516-26. doi: 10.1016/j.bbadis.2012.05.007. Epub 2012 May 18.
- Deficiency of UDP-galactose 4'-epimerase is implicated in type III galactosemia. Two variants, p.K161N-hGALE and p.D175N-hGALE, have been previously found in combination with other alleles in patients with a mild form of the disease. Both variants were studied in vivo and in vitro and showed differe
- PMID 22613355
Japanese Journal
- Molecular characterization of galactokinase deficiency in Japanese patients
- ガラクトース血症II型の遺伝子解析(第5報) : DGGE法による変異スクリーニング
Related Links
- Frequency United States Traditionally, most newborn screening programs were designed to identify transferase deficiency; consequently, accumulated galactose in submitted blood samples could be missed. [3] However ...
- Clinical Synopsis TEXT A number sign (#) is used with this entry because galactokinase deficiency is caused by homozygous or heterozygous mutation in the GALK1 gene (604313) on chromosome 17q24. Classic galactosemia (230400 ...
Related Pictures
★リンクテーブル★
[★]
- 英
- galactokinase deficiency
- 同
- galactokinase欠損症、GALK欠損症 GALK deficiency
- 関
- ガラクトース血症
[★]
- 不足、欠乏、欠失、欠如、欠損、不十分。栄養不足、栄養素欠乏、欠乏症。(遺伝子)(染色体内の)遺伝子欠失
- 欠けているもの、不足している物。不足分。不完全なもの、欠点のあるもの
- 関
- absence, agenesis, dearth, defect, defective, deficient, deficit, delete, deletion, deletional, depletion, deprivation, deprive, lack, miss, missing, morphological defect, paucity, scarce, scarcity, starve