The natural history of classic galactosemia: Lessons from the GalNet registry

M. E. Rubio-Gozalbo, M. Haskovic, A. M. Bosch, B. Burnyte, A. I. Coelho, D. Cassiman, M. L. Couce, C. Dawson, D. Demirbas, T. Derks, F. Eyskens, M. T. Forga, S. Grunewald, J. Häberle, M. Hochuli, A. Hubert, H. H. Huidekoper, P. Janeiro, J. Kotzka, I. Knerr & 23 others P. Labrune, Y. E. Landau, J. G. Langendonk, D. Möslinger, D. Müller-Wieland, E. Murphy, K. Õunap, D. Ramadza, I. A. Rivera, S. Scholl-Buergi, K. M. Stepien, A. Thijs, C. Tran, R. Vara, G. Visser, R. Vos, M. de Vries, S. E. Waisbren, M. M. Welsink-Karssies, S. B. Wortmann, M. Gautschi, E. P. Treacy, G. T. Berry

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set.
Original languageEnglish
Article number86
JournalOrphanet Journal of Rare Diseases
Volume14
Issue number1
DOIs
Publication statusPublished - 2019

Cite this

Rubio-Gozalbo, M. E., Haskovic, M., Bosch, A. M., Burnyte, B., Coelho, A. I., Cassiman, D., ... Berry, G. T. (2019). The natural history of classic galactosemia: Lessons from the GalNet registry. Orphanet Journal of Rare Diseases, 14(1), [86]. https://doi.org/10.1186/s13023-019-1047-z
Rubio-Gozalbo, M. E. ; Haskovic, M. ; Bosch, A. M. ; Burnyte, B. ; Coelho, A. I. ; Cassiman, D. ; Couce, M. L. ; Dawson, C. ; Demirbas, D. ; Derks, T. ; Eyskens, F. ; Forga, M. T. ; Grunewald, S. ; Häberle, J. ; Hochuli, M. ; Hubert, A. ; Huidekoper, H. H. ; Janeiro, P. ; Kotzka, J. ; Knerr, I. ; Labrune, P. ; Landau, Y. E. ; Langendonk, J. G. ; Möslinger, D. ; Müller-Wieland, D. ; Murphy, E. ; Õunap, K. ; Ramadza, D. ; Rivera, I. A. ; Scholl-Buergi, S. ; Stepien, K. M. ; Thijs, A. ; Tran, C. ; Vara, R. ; Visser, G. ; Vos, R. ; de Vries, M. ; Waisbren, S. E. ; Welsink-Karssies, M. M. ; Wortmann, S. B. ; Gautschi, M. ; Treacy, E. P. ; Berry, G. T. / The natural history of classic galactosemia: Lessons from the GalNet registry. In: Orphanet Journal of Rare Diseases. 2019 ; Vol. 14, No. 1.
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title = "The natural history of classic galactosemia: Lessons from the GalNet registry",
abstract = "Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8{\%}) and despite following a diet developed brain impairments (85.0{\%}), primary ovarian insufficiency (79.7{\%}) and a diminished bone mineral density (26.5{\%}). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1{\%} and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set.",
author = "Rubio-Gozalbo, {M. E.} and M. Haskovic and Bosch, {A. M.} and B. Burnyte and Coelho, {A. I.} and D. Cassiman and Couce, {M. L.} and C. Dawson and D. Demirbas and T. Derks and F. Eyskens and Forga, {M. T.} and S. Grunewald and J. H{\"a}berle and M. Hochuli and A. Hubert and Huidekoper, {H. H.} and P. Janeiro and J. Kotzka and I. Knerr and P. Labrune and Landau, {Y. E.} and Langendonk, {J. G.} and D. M{\"o}slinger and D. M{\"u}ller-Wieland and E. Murphy and K. {\~O}unap and D. Ramadza and Rivera, {I. A.} and S. Scholl-Buergi and Stepien, {K. M.} and A. Thijs and C. Tran and R. Vara and G. Visser and R. Vos and {de Vries}, M. and Waisbren, {S. E.} and Welsink-Karssies, {M. M.} and Wortmann, {S. B.} and M. Gautschi and Treacy, {E. P.} and Berry, {G. T.}",
year = "2019",
doi = "10.1186/s13023-019-1047-z",
language = "English",
volume = "14",
journal = "Orphanet Journal of Rare Diseases",
issn = "1750-1172",
publisher = "BioMed Central",
number = "1",

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Rubio-Gozalbo, ME, Haskovic, M, Bosch, AM, Burnyte, B, Coelho, AI, Cassiman, D, Couce, ML, Dawson, C, Demirbas, D, Derks, T, Eyskens, F, Forga, MT, Grunewald, S, Häberle, J, Hochuli, M, Hubert, A, Huidekoper, HH, Janeiro, P, Kotzka, J, Knerr, I, Labrune, P, Landau, YE, Langendonk, JG, Möslinger, D, Müller-Wieland, D, Murphy, E, Õunap, K, Ramadza, D, Rivera, IA, Scholl-Buergi, S, Stepien, KM, Thijs, A, Tran, C, Vara, R, Visser, G, Vos, R, de Vries, M, Waisbren, SE, Welsink-Karssies, MM, Wortmann, SB, Gautschi, M, Treacy, EP & Berry, GT 2019, 'The natural history of classic galactosemia: Lessons from the GalNet registry' Orphanet Journal of Rare Diseases, vol. 14, no. 1, 86. https://doi.org/10.1186/s13023-019-1047-z

The natural history of classic galactosemia: Lessons from the GalNet registry. / Rubio-Gozalbo, M. E.; Haskovic, M.; Bosch, A. M.; Burnyte, B.; Coelho, A. I.; Cassiman, D.; Couce, M. L.; Dawson, C.; Demirbas, D.; Derks, T.; Eyskens, F.; Forga, M. T.; Grunewald, S.; Häberle, J.; Hochuli, M.; Hubert, A.; Huidekoper, H. H.; Janeiro, P.; Kotzka, J.; Knerr, I.; Labrune, P.; Landau, Y. E.; Langendonk, J. G.; Möslinger, D.; Müller-Wieland, D.; Murphy, E.; Õunap, K.; Ramadza, D.; Rivera, I. A.; Scholl-Buergi, S.; Stepien, K. M.; Thijs, A.; Tran, C.; Vara, R.; Visser, G.; Vos, R.; de Vries, M.; Waisbren, S. E.; Welsink-Karssies, M. M.; Wortmann, S. B.; Gautschi, M.; Treacy, E. P.; Berry, G. T.

In: Orphanet Journal of Rare Diseases, Vol. 14, No. 1, 86, 2019.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - The natural history of classic galactosemia: Lessons from the GalNet registry

AU - Rubio-Gozalbo, M. E.

AU - Haskovic, M.

AU - Bosch, A. M.

AU - Burnyte, B.

AU - Coelho, A. I.

AU - Cassiman, D.

AU - Couce, M. L.

AU - Dawson, C.

AU - Demirbas, D.

AU - Derks, T.

AU - Eyskens, F.

AU - Forga, M. T.

AU - Grunewald, S.

AU - Häberle, J.

AU - Hochuli, M.

AU - Hubert, A.

AU - Huidekoper, H. H.

AU - Janeiro, P.

AU - Kotzka, J.

AU - Knerr, I.

AU - Labrune, P.

AU - Landau, Y. E.

AU - Langendonk, J. G.

AU - Möslinger, D.

AU - Müller-Wieland, D.

AU - Murphy, E.

AU - Õunap, K.

AU - Ramadza, D.

AU - Rivera, I. A.

AU - Scholl-Buergi, S.

AU - Stepien, K. M.

AU - Thijs, A.

AU - Tran, C.

AU - Vara, R.

AU - Visser, G.

AU - Vos, R.

AU - de Vries, M.

AU - Waisbren, S. E.

AU - Welsink-Karssies, M. M.

AU - Wortmann, S. B.

AU - Gautschi, M.

AU - Treacy, E. P.

AU - Berry, G. T.

PY - 2019

Y1 - 2019

N2 - Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set.

AB - Background: Classic galactosemia is a rare inborn error of carbohydrate metabolism, caused by a severe deficiency of the enzyme galactose-1-phosphate uridylyltransferase (GALT). A galactose-restricted diet has proven to be very effective to treat the neonatal life-threatening manifestations and has been the cornerstone of treatment for this severe disease. However, burdensome complications occur despite a lifelong diet. For rare diseases, a patient disease specific registry is fundamental to monitor the lifespan pathology and to evaluate the safety and efficacy of potential therapies. In 2014, the international Galactosemias Network (GalNet) developed a web-based patient registry for this disease, the GalNet Registry. The aim was to delineate the natural history of classic galactosemia based on a large dataset of patients. Methods: Observational data derived from 15 countries and 32 centers including 509 patients were acquired between December 2014 and July 2018. Results: Most affected patients experienced neonatal manifestations (79.8%) and despite following a diet developed brain impairments (85.0%), primary ovarian insufficiency (79.7%) and a diminished bone mineral density (26.5%). Newborn screening, age at onset of dietary treatment, strictness of the galactose-restricted diet, p.Gln188Arg mutation and GALT enzyme activity influenced the clinical picture. Detection by newborn screening and commencement of diet in the first week of life were associated with a more favorable outcome. A homozygous p.Gln188Arg mutation, GALT enzyme activity of ≤ 1% and strict galactose restriction were associated with a less favorable outcome. Conclusion: This study describes the natural history of classic galactosemia based on the hitherto largest data set.

UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85064994284&origin=inward

UR - https://www.ncbi.nlm.nih.gov/pubmed/31029175

U2 - 10.1186/s13023-019-1047-z

DO - 10.1186/s13023-019-1047-z

M3 - Article

VL - 14

JO - Orphanet Journal of Rare Diseases

JF - Orphanet Journal of Rare Diseases

SN - 1750-1172

IS - 1

M1 - 86

ER -