| 1. |
- Blomquist, H K, et al.
(författare)
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Glycerol kinase deficiency in two brothers with and without clinical manifestations.
- 1996
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Ingår i: Clinical genetics. - 0009-9163 .- 1399-0004. ; 50:5, s. 375-9
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Tidskriftsartikel (refereegranskat)abstract
- We report two brothers with glycerol kinase deficiency (GKD). The older brother had serious clinical symptoms, mental and growth retardation, abnormal skeleton, spontaneous fractures and premature loss of abnormal teeth. He and his mother had low serum phosphate levels. He had elevated serum and urine glycerol levels and GKD was found in cultured fibroblasts. Prenatal diagnosis was performed in the second pregnancy. Glycerol kinase activity was considered normal in a chorionic villus sample of the foetus. After birth, it was found that the boy had elevated serum and urine glycerol levels. Enzymatic analysis in cultured fibroblasts revealed that this boy also had GKD, in spite of having no expression of the disease. Chromosomal analyses in the parents and both boys were normal. Major rearrangements or deletions were not detected in molecular studies of DNA from the two brothers. The hybridisation pattern was normal and no allelic loss was observed.
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| 2. |
- Børresen, A L, et al.
(författare)
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Prenatal diagnosis of glycerol-kinase deficiency associated with a DNA deletion on the short arm of the X-chromosome.
- 1987
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Ingår i: Clinical genetics. - 0009-9163. ; 32:4, s. 254-9
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Tidskriftsartikel (refereegranskat)abstract
- Amniocentesis was performed in a woman who previously had given birth to a boy who died at 12 months of age with a diagnosis of glyceroluria and adrenal insufficiency. A high amount of glycerol (9.0 standard deviations above mean for controls) was found in the amniotic fluid. Enzyme activity of glycerol-kinase (ATP:glycerol-3-phosphotransferase, EC 2.7.1.30) in the cultured amniotic fluid cells was very low. The pregnancy was terminated and a male fetus was aborted. Examinations of DNA isolated from the fetus did demonstrate deletions of two out of 16 DNA probes mapping to the short arm of the X-chromosome. The probes failing to hybridize to DNA from the fetus were C7 (DXS28) and L1.4 (DXS68), both mapping to Xp21.3 and located terminal to the Duchenne locus.
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| 3. |
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| 4. |
- Fodor, Enikö, et al.
(författare)
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Glycerolkinasbrist med symtomdebut i vuxen ålder. Ovanlig orsak till koma, metabol acidos, hypoglykemi och hypotermi : [Glycerol kinase deficiency with debut of symptoms in adult age. Unusual cause of coma, metabolic acidosis, hypoglycemia and hypothermia]
- 2010
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Ingår i: Läkartidningen. - 0023-7205. ; 107:40, s. 2408-2410
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Tidskriftsartikel (refereegranskat)abstract
- Glycerolkinasbrist är en mycket ovanlig X-bunden recessiv sjukdom. Vi rapporterar här ett fall av nyupptäckt isolerad glycerolkinasbrist hos en vuxen man, som insjuknade med fulminanta och intensivvårdskrävande symtom i form av koma, grav metabol acidos, hypoglykemi och hypotermi. Sjukdomsbilden var associerad med en – för första gången beskriven – punktmutation, C332A, i exon 4 i glycerolkinasgenen.
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| 5. |
- Fodor, Enikö, et al.
(författare)
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Glycerolkinasbrist med symtomdebut i vuxen ålder. Ovanlig orsak till koma, metabol acidos, hypoglykemi och hypotermi
- 2010
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Ingår i: Läkartidningen. - 1652-7518 .- 0023-7205. ; 107:40, s. 2408-2410
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Tidskriftsartikel (refereegranskat)abstract
- Glycerolkinasbrist är en mycket ovanlig X-bunden recessiv sjukdom.Vi rapporterar här ett fall av nyupptäckt isolerad glycerolkinasbrist hos en vuxen man, som insjuknade med fulminanta och intensivvårdskrävande symtom i form av koma, grav metabol acidos, hypoglykemi och hypotermi.Sjukdomsbilden var associerad med en – för första gången beskriven – punktmutation, C332A, i exon 4 i glycerolkinasgenen.
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| 6. |
- Hellerud, Christina, 1955, et al.
(författare)
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Clinical heterogeneity and molecular findings in five Polish patients with glycerol kinase deficiency: investigation of two splice site mutations with computerized splice junction analysis and Xp21 gene-specific mRNA analysis.
- 2003
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Ingår i: Molecular genetics and metabolism. - 1096-7192. ; 79:3, s. 149-59
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Tidskriftsartikel (refereegranskat)abstract
- Five cases of glycerol kinase deficiency are presented with clinical, biochemical, and genetic results. Two had the glycerol kinase deficiency as part of an Xp21 contiguous gene deletion syndrome-complex form-and three had an isolated form of the enzyme deficiency. In these we found two splice site mutations (IVS1+4A>G, IVS9-1G>T) and one insertion (1393_1394insG). In patients with the complex form, a deletion of the DAX1, GK genes and the distal part of the DMD gene was found. A computerized study was performed to predict the effects of the splice site mutations. It showed that the IVS9-1G>T mutation substantially altered and removed the wild-type site and enhanced a cryptic site seven nucleotides downstream, and that the IVS1+4A>G diminished the strength of the wild-type donor site from strong to leaky. To verify these predictions, we developed an RT-PCR system with gene-specific primers that exclusively amplifies the Xp21 glycerol kinase gene transcript. Identification of individuals at risk is motivated by a need to avoid delay in a correct diagnosis. For reliable identification of heterozygotes for isolated glycerol kinase deficiency, knowledge of the specific mutation in the proband is required. This is easily obtained with the RT-PCR analyses developed in this study.
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| 7. |
- Hellerud, Christina, 1955
(författare)
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Glycerol kinase deficiency. Clinical, biochemical, and genetic aspects
- 2004
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Glycerol kinase deficiency (GKD, MIM 307030) is an X-linked recessive inborn error of metabolism occurring isolated or in an Xp contiguous gene syndrome with adrenal hypoplasia and/or Duchenne muscular dystrophy. The gene syndrome is due to deletions in the p21 region on the X chromosome. Children with deletions often present in early age with salt wasting and hypoglycaemia. Children with isolated GKD have hypoglycaemic symptoms with or without low blood glucose concentration and pronounced ketonemia in conjunction with infections or after physical exercise. The discrepancy between the severity of symptoms and the concurrent infection is of diagnostic value. Adult individuals with GKD have no similar symptoms. Individuals with GKD have a glycerol concentration of 2 to 8 mmol/L in plasma and excrete all glycerol from lipolysis into the urine (100-300 mmol/L, 10-30 g/24 h). Most triglyceride methods used in routine laboratories measure the amount of glycerol after hydrolysis and results in falsely reported elevated triglycerides in these patients. We have established methods to identify GKD as part of the Xp contiguous gene syndrome and an mRNA analysis to detect the glycerol kinase (GK) transcript from the Xp21 locus, enabling us to identify the genetic aberration. We have identified thirteen new mutations in the GK gene, used splice-junction analysis and molecular modelling to investigate the effect on the protein.The first individual (a 10-year-old boy) with symptoms from isolated GKD was described in 1983. We have followed him and another similar case into adulthood. Controlled fasting provocations and exercise tests were performed in childhood and repeated at adult age. We suggest that the greater importance of glycerol as a gluconeogenetic substrate in children than in adults, explains the hypoglycaemic episodes in the young GKD patient. With frequent carbohydrate-rich meals, carbohydrates with a low glycemic index, food or glucose when symptoms arise, extra food before and after physical activity, the prognosis is good.It is important to identify individuals at risk. Our studies have shown the need for a genetic analysis to distinguish between carriers and non-carriers, as the level of glycerol in plasma and urine or activity of GK can not discriminate.
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| 8. |
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| 9. |
- Hellerud, Christina, 1955, et al.
(författare)
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Glycerol metabolism and the determination of triglycerides--clinical, biochemical and molecular findings in six subjects.
- 2003
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Ingår i: Clinical chemistry and laboratory medicine : CCLM / FESCC. - 1434-6621. ; 41:1, s. 46-55
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Tidskriftsartikel (refereegranskat)abstract
- Recent recommendations in the National Cholesterol Education Program Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (ATPIII) are expected to increase the number of triglyceride (TG) determinations and consequently the risk of misinterpretation of "non-blanked" results with co-determination of free glycerol. Glycerol-kinase deficiency (GKD) is one cause of falsely elevated TG results. The natural history of isolated GKD with symptom-free cases and cases with e.g. severe episodes of hypoglycemia and/or ketoacidosis challenges the laboratories to identify cases of GKD and family members at risk. "Blanked" methods reporting both glycerol and TG concentration are therefore desirable. Molecular studies of the glycerol kinase (GK) and DAX1 genes were performed on four cases of "persistent hypertriglyceridemia" found in an Italian population and on two pediatric cases with high serum glycerol concentration. Two new missense mutations were found (C358Y, T961). Molecular modeling on GK from E. coli, indicate that these mutations are located in parts of the enzyme important for enzyme formation or activity. One splice-site mutation, (IVS9A-1G>A), was found in two brothers. Splice-junction analysis indicates that it destroys the splice site and results in a mixture of mRNA. Deletion of the GK and DAX1 genes was found in one child with symptoms of adrenal failure. A female with glycerolemia and glyceroluria had normal GK activity but possibly slightly decreased ability to oxidize glycerol.
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| 10. |
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