Galactokinase deficiency: lessons from the GalNet registry

M. Estela Rubio-Gozalbo; Britt Derks; Anibh Martin Das; Uta Meyer; Dorothea Möslinger; M. Luz Couce; Aurélie Empain; Can Ficicioglu; Natalia Juliá Palacios; Mariela M. De Los Santos De Pelegrin; Isabel A. Rivera; Sabine Scholl-Bürgi; Annet M. Bosch; David Cassiman; Didem Demirbas; Matthias Gautschi; Ina Knerr; Philippe Labrune; Anastasia Skouma; Patrick Verloo; Saskia B. Wortmann; Eileen P. Treacy; David J. Timson; Gerard T. Berry

doi:10.1038/s41436-020-00942-9

Galactokinase deficiency: lessons from the GalNet registry

M. Estela Rubio-Gozalbo, Britt Derks, Anibh Martin Das, Uta Meyer, Dorothea Möslinger, M. Luz Couce, Aurélie Empain, Can Ficicioglu, Natalia Juliá Palacios, Mariela M. De Los Santos De Pelegrin, Isabel A. Rivera, Sabine Scholl-Bürgi, Annet M. Bosch, David Cassiman, Didem Demirbas, Matthias Gautschi, Ina Knerr, Philippe Labrune, Anastasia Skouma, Patrick VerlooSaskia B. Wortmann, Eileen P. Treacy, David J. Timson, Gerard T. Berry

University of Brighton

Research output: Contribution to journal › Article › peer-review

Abstract

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 Eleven different genotypes were described, including six unpublished variants.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.

Original language	English
Pages (from-to)	202-210
Number of pages	9
Journal	Genetics in Medicine
Volume	23
Issue number	1
DOIs	https://doi.org/10.1038/s41436-020-00942-9
Publication status	Published - 18 Aug 2020

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This article is licensed under a Creative Commons
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party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

Keywords

cataract
galactokinase 1 deficiency
GALK1 gene variants
galactosemias registry
neonatal complications

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1-s2.0-S2211320720300245-mainFinal published version, 6.15 MBLicence: CC BY-NC-ND

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Rubio-Gozalbo, M. E., Derks, B., Das, A. M., Meyer, U., Möslinger, D., Couce, M. L., Empain, A., Ficicioglu, C., Juliá Palacios, N., De Los Santos De Pelegrin, M. M., Rivera, I. A., Scholl-Bürgi, S., Bosch, A. M., Cassiman, D., Demirbas, D., Gautschi, M., Knerr, I., Labrune, P., Skouma, A., ... Berry, G. T. (2020). Galactokinase deficiency: lessons from the GalNet registry. Genetics in Medicine, 23(1), 202-210. https://doi.org/10.1038/s41436-020-00942-9

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abstract = "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.",

keywords = "cataract, galactokinase 1 deficiency, GALK1 gene variants, galactosemias registry, neonatal complications",

author = "Rubio-Gozalbo, {M. Estela} and Britt Derks and Das, {Anibh Martin} and Uta Meyer and Dorothea M{\"o}slinger and Couce, {M. Luz} and Aur{\'e}lie Empain and Can Ficicioglu and {Juli{\'a} Palacios}, Natalia and {De Los Santos De Pelegrin}, {Mariela M.} and Rivera, {Isabel A.} and Sabine Scholl-B{\"u}rgi and Bosch, {Annet M.} and David Cassiman and Didem Demirbas and Matthias Gautschi and Ina Knerr and Philippe Labrune and Anastasia Skouma and Patrick Verloo and Wortmann, {Saskia B.} and Treacy, {Eileen P.} and Timson, {David J.} and Berry, {Gerard T.}",

note = "This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article{\textquoteright}s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article{\textquoteright}s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/",

year = "2020",

month = aug,

day = "18",

doi = "10.1038/s41436-020-00942-9",

language = "English",

volume = "23",

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journal = "Genetics in Medicine",

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Rubio-Gozalbo, ME, Derks, B, Das, AM, Meyer, U, Möslinger, D, Couce, ML, Empain, A, Ficicioglu, C, Juliá Palacios, N, De Los Santos De Pelegrin, MM, Rivera, IA, Scholl-Bürgi, S, Bosch, AM, Cassiman, D, Demirbas, D, Gautschi, M, Knerr, I, Labrune, P, Skouma, A, Verloo, P, Wortmann, SB, Treacy, EP, Timson, DJ & Berry, GT 2020, 'Galactokinase deficiency: lessons from the GalNet registry', Genetics in Medicine, vol. 23, no. 1, pp. 202-210. https://doi.org/10.1038/s41436-020-00942-9

TY - JOUR

T1 - Galactokinase deficiency

T2 - lessons from the GalNet registry

AU - Rubio-Gozalbo, M. Estela

AU - Derks, Britt

AU - Das, Anibh Martin

AU - Meyer, Uta

AU - Möslinger, Dorothea

AU - Couce, M. Luz

AU - Empain, Aurélie

AU - Ficicioglu, Can

AU - Juliá Palacios, Natalia

AU - De Los Santos De Pelegrin, Mariela M.

AU - Rivera, Isabel A.

AU - Scholl-Bürgi, Sabine

AU - Bosch, Annet M.

AU - Cassiman, David

AU - Demirbas, Didem

AU - Gautschi, Matthias

AU - Knerr, Ina

AU - Labrune, Philippe

AU - Skouma, Anastasia

AU - Verloo, Patrick

AU - Wortmann, Saskia B.

AU - Treacy, Eileen P.

AU - Timson, David J.

AU - Berry, Gerard T.

N1 - This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/

PY - 2020/8/18

Y1 - 2020/8/18

N2 - 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.

AB - 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.

KW - cataract

KW - galactokinase 1 deficiency

KW - GALK1 gene variants

KW - galactosemias registry

KW - neonatal complications

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U2 - 10.1038/s41436-020-00942-9

DO - 10.1038/s41436-020-00942-9

M3 - Article

AN - SCOPUS:85089519835

SN - 1098-3600

VL - 23

SP - 202

EP - 210

JO - Genetics in Medicine

JF - Genetics in Medicine

IS - 1

ER -

Galactokinase deficiency: lessons from the GalNet registry

Abstract

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Keywords

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