Galactokinase deficiency : lessons from the GalNet registry
PURPOSE: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype.
METHODS: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020.
RESULTS: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial.
CONCLUSION: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2021 |
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| Erschienen: |
2021 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:23 |
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| Enthalten in: |
Genetics in medicine : official journal of the American College of Medical Genetics - 23(2021), 1 vom: 19. Jan., Seite 202-210 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Rubio-Gozalbo, M Estela [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 03.06.2021 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1038/s41436-020-00942-9 |
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| funding: |
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|---|---|
| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM313825335 |
|---|
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| 024 | 7 | |a 10.1038/s41436-020-00942-9 |2 doi | |
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| 100 | 1 | |a Rubio-Gozalbo, M Estela |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Galactokinase deficiency |b lessons from the GalNet registry |
| 264 | 1 | |c 2021 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 03.06.2021 | ||
| 500 | |a Date Revised 31.05.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a PURPOSE: Galactokinase (GALK1) deficiency is a rare hereditary galactose metabolism disorder. Beyond cataract, the phenotypic spectrum is questionable. Data from affected patients included in the Galactosemias Network registry were collected to better characterize the phenotype | ||
| 520 | |a METHODS: Observational study collecting medical data of 53 not previously reported GALK1 deficient patients from 17 centers in 11 countries from December 2014 to April 2020 | ||
| 520 | |a RESULTS: Neonatal or childhood cataract was reported in 15 and 4 patients respectively. The occurrence of neonatal hypoglycemia and infection were comparable with the general population, whereas bleeding diathesis (8.1% versus 2.17-5.9%) and encephalopathy (3.9% versus 0.3%) were reported more often. Elevated transaminases were seen in 25.5%. Cognitive delay was reported in 5 patients. Urinary galactitol was elevated in all patients at diagnosis; five showed unexpected Gal-1-P increase. Most patients showed enzyme activities ≤1%. Eleven different genotypes were described, including six unpublished variants. The majority was homozygous for NM_000154.1:c.82C>A (p.Pro28Thr). Thirty-five patients were diagnosed following newborn screening, which was clearly beneficial | ||
| 520 | |a CONCLUSION: The phenotype of GALK1 deficiency may include neonatal elevation of transaminases, bleeding diathesis, and encephalopathy in addition to cataract. Potential complications beyond the neonatal period are not systematically surveyed and a better delineation is needed | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Observational Study | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a GALK1 gene variants; neonatal complications | |
| 650 | 4 | |a cataract; galactosemias registry | |
| 650 | 4 | |a galactokinase 1 deficiency | |
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| 700 | 1 | |a Derks, Britt |e verfasserin |4 aut | |
| 700 | 1 | |a Das, Anibh Martin |e verfasserin |4 aut | |
| 700 | 1 | |a Meyer, Uta |e verfasserin |4 aut | |
| 700 | 1 | |a Möslinger, Dorothea |e verfasserin |4 aut | |
| 700 | 1 | |a Couce, M Luz |e verfasserin |4 aut | |
| 700 | 1 | |a Empain, Aurélie |e verfasserin |4 aut | |
| 700 | 1 | |a Ficicioglu, Can |e verfasserin |4 aut | |
| 700 | 1 | |a Juliá Palacios, Natalia |e verfasserin |4 aut | |
| 700 | 1 | |a De Los Santos De Pelegrin, Mariela M |e verfasserin |4 aut | |
| 700 | 1 | |a Rivera, Isabel A |e verfasserin |4 aut | |
| 700 | 1 | |a Scholl-Bürgi, Sabine |e verfasserin |4 aut | |
| 700 | 1 | |a Bosch, Annet M |e verfasserin |4 aut | |
| 700 | 1 | |a Cassiman, David |e verfasserin |4 aut | |
| 700 | 1 | |a Demirbas, Didem |e verfasserin |4 aut | |
| 700 | 1 | |a Gautschi, Matthias |e verfasserin |4 aut | |
| 700 | 1 | |a Knerr, Ina |e verfasserin |4 aut | |
| 700 | 1 | |a Labrune, Philippe |e verfasserin |4 aut | |
| 700 | 1 | |a Skouma, Anastasia |e verfasserin |4 aut | |
| 700 | 1 | |a Verloo, Patrick |e verfasserin |4 aut | |
| 700 | 1 | |a Wortmann, Saskia B |e verfasserin |4 aut | |
| 700 | 1 | |a Treacy, Eileen P |e verfasserin |4 aut | |
| 700 | 1 | |a Timson, David J |e verfasserin |4 aut | |
| 700 | 1 | |a Berry, Gerard T |e verfasserin |4 aut | |
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