Clinical and biochemical evolution after partial dietary liberalization of two cases of galactosemia due to galactose mutarotase deficiency.
GALM deficiency
Galactose mutarotase deficiency
Type IV galactosemia
Journal
BMC pediatrics
ISSN: 1471-2431
Titre abrégé: BMC Pediatr
Pays: England
ID NLM: 100967804
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
26
02
2024
accepted:
10
09
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
30
9
2024
Statut:
epublish
Résumé
The recommended diet attitude in the recently described galactose mutarotase (GALM) deficiency is not yet established. We describe two 9-years twins who remain asymptomatic despite prolonged partial dietary liberalization from 18 months of age, after two periods of galactose-free diet. It represents the second report in Europe of GALM deficiency. Two male monochorionic diamniotic twins were detected through newborn screening by galactosuria and increased total blood galactose. They started galactose dietary restriction with biochemical normalization. After exclusion of the three previously described types of galactosemia, a progressively galactose reintroduction was initiated. The clinical follow-up developed include neurological assessment and intelligence quotient, annual ophthalmological evaluation and biannual abdominal ultrasound; whereas the biochemical assessment comprises quarterly determinations of galactose 1-phosphate and galactosuria and annual determination of liver and renal function, 25-OH-vitamin D and calcium levels. Sanger sequencing of GALM gene was complemented by the study of gene dose using SNPs array and a protein modeling to study the conformational changes induced in GALM protein. In both siblings a novel and complete deletion of exon 4 in GALM gene was detected. Both remained asymptomatic, with normal growth and intellectual development, despite dietary liberalization. Evolutionarily, the biochemical profile in blood remained normal with intermittent galactosuria. The absence of clinical involvement after 7 years of dietary liberalization is interesting to expand the knowledge about the recommended dietary management in this pathology.
Sections du résumé
BACKGROUND
BACKGROUND
The recommended diet attitude in the recently described galactose mutarotase (GALM) deficiency is not yet established. We describe two 9-years twins who remain asymptomatic despite prolonged partial dietary liberalization from 18 months of age, after two periods of galactose-free diet. It represents the second report in Europe of GALM deficiency.
CASE PRESENTATION
METHODS
Two male monochorionic diamniotic twins were detected through newborn screening by galactosuria and increased total blood galactose. They started galactose dietary restriction with biochemical normalization. After exclusion of the three previously described types of galactosemia, a progressively galactose reintroduction was initiated. The clinical follow-up developed include neurological assessment and intelligence quotient, annual ophthalmological evaluation and biannual abdominal ultrasound; whereas the biochemical assessment comprises quarterly determinations of galactose 1-phosphate and galactosuria and annual determination of liver and renal function, 25-OH-vitamin D and calcium levels. Sanger sequencing of GALM gene was complemented by the study of gene dose using SNPs array and a protein modeling to study the conformational changes induced in GALM protein. In both siblings a novel and complete deletion of exon 4 in GALM gene was detected. Both remained asymptomatic, with normal growth and intellectual development, despite dietary liberalization. Evolutionarily, the biochemical profile in blood remained normal with intermittent galactosuria.
CONCLUSIONS
CONCLUSIONS
The absence of clinical involvement after 7 years of dietary liberalization is interesting to expand the knowledge about the recommended dietary management in this pathology.
Identifiants
pubmed: 39350089
doi: 10.1186/s12887-024-05074-6
pii: 10.1186/s12887-024-05074-6
doi:
Substances chimiques
Galactose
X2RN3Q8DNE
galactose mutarotase
EC 5.1.3.3
Carbohydrate Epimerases
EC 5.1.3.-
Types de publication
Journal Article
Case Reports
Langues
eng
Sous-ensembles de citation
IM
Pagination
620Informations de copyright
© 2024. The Author(s).
Références
Leloir LF. Two decades of research on the biosynthesis of saccharides. Science. 1971;172(3990):1299–303. https://doi.org/10.1126/science.172.3990.1299 .
doi: 10.1126/science.172.3990.1299
pubmed: 4325519
Yazici H, Canda E, Altınok YA, Ucar SK, Coker M. Two siblings with galactose mutarotase deficiency: clinical differences. JIMD Rep. 2021;63(1):25–8. https://doi.org/10.1002/jmd2.12263 .
doi: 10.1002/jmd2.12263
pubmed: 35028268
pmcid: 8743342
Wada Y, Kikuchi A, Arai-Ichinoi N, Sakamoto O, Takezawa Y, Iwasawa S, et al. Biallelic GALM pathogenic variants cause a novel type of galactosemia. Genet Med. 2019;21(6):1286–94. https://doi.org/10.1038/s41436-018-0340-x .
doi: 10.1038/s41436-018-0340-x
pubmed: 30451973
Thoden JB, Timson D, Reece RJ, Holden HM. Molecular structure of human galactose mutarotase. J Biol Chem. 2004;279(22):23431–7. https://doi.org/10.1074/jbc.M402347200 .
doi: 10.1074/jbc.M402347200
pubmed: 15026423
Banford S, Timson DJ. The structural and molecular biology of type IV galactosemia. Biochimie. 2021;183:13–7. https://doi.org/10.1016/j.biochi.2020.11.001 .
doi: 10.1016/j.biochi.2020.11.001
pubmed: 33181226
Timson DJ, Type IV galactosemia. Genet Med. 2019;6:1283–5. https://doi.org/10.1038/s41436-018-0359-z .
doi: 10.1038/s41436-018-0359-z
Jensen UG, Brandt NJ, Cristensen E, Skoubye F, Norgrard-Pedersen B, Simonsen H. Neonatal screening for galactosemias by quantitative analysis of hexose monophosphates using tandem mass spectrometry. A retrospective study. Clin Chem. 2001;47:1364–72.
doi: 10.1093/clinchem/47.8.1364
pubmed: 11468223
Alonso-Fernández JR, Bóveda MD, Parrado C, Peña J, Fraga JM. Continuous thin-layer chromatography of sugars of clinical interest in samples of urine impregnated on paper. J Chromatogr. 1981;217357–366. https://doi.org/10.1016/s0021-9673(00)88090-5 .
Iwasawa S, Kikuchi A, Wada Y, Arai-Ichinoi N, Sakamoto O, Tamiya G, et al. The prevalence of GALM mutations that cause galactosemia: a database of functionally evaluated variants. Mol Genet Metab. 2019;126(4):362–7. https://doi.org/10.1016/j.ymgme.2019.01.018 .
doi: 10.1016/j.ymgme.2019.01.018
pubmed: 30910422
Mikami-Saito Y, Wada Y, Arai-Ichinoi N, Nakajima Y, Suzuki-Ajihara S, Murayama K, et al. Phenotypic and genetic spectra of galactose mutarotase deficiency: a nationwide survey conducted in Japan. Genet Med. 2024;26(8):101165. https://doi.org/10.1016/j.gim.2024.101165 .
doi: 10.1016/j.gim.2024.101165
pubmed: 38762772
Kikuchi A, Wada Y, Ohura T, Kure S. The Discovery of GALM Deficiency (type IV Galactosemia) and newborn screening system for Galactosemia in Japan. Int J Neonatal Screen. 2021;25(4):68. https://doi.org/10.3390/ijns7040068 .
doi: 10.3390/ijns7040068
Wada Y, Arai-Ichinoi N, Kikuchi A, Kure S. β-Galactosidase therapy can mitigate blood galactose elevation after an oral lactose load in galactose mutarotase deficiency. J Inherit Metab Dis. 2022;45(2):334–9. https://doi.org/10.1002/jimd.12444 .
doi: 10.1002/jimd.12444
pubmed: 34611916
Wada Y, Kikuchi A, Arai-Ichinoi N, Sakamoto O, Takezawa Y, Iwasawa S, Niihori T, et al. Correction: Biallelic GALM pathogenic variants cause a novel type of galactosemia. Genet Med. 2020;22(7):1281. https://doi.org/10.1038/s41436-020-0836-z . Erratum for: Genet Med. 2019;21(6):1286–1294.
doi: 10.1038/s41436-020-0836-z
pubmed: 32499603