The Galactose Index measured in fibroblasts of GALT deficient patients distinguishes variant patients detected by newborn screening from patients with classical phenotypes

The high variability in clinical outcome of patients with Classical Galactosemia (CG) is poorly understood and underlines the importance of prognostic biomarkers, which are currently lacking. The aim of this study was to investigate if residual galactose metabolism capacity is associated with clinic...

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Bibliographic Details
Published in:Molecular genetics and metabolism 2020-03, Vol.129 (3), p.171-176
Main Authors: Welsink-Karssies, Mendy M., van Weeghel, Michel, Hollak, Carla E.M., Elfrink, Hyung L., Janssen, Mirian C.H., Lai, Kent, Langendonk, Janneke G., Oussoren, Esmee, Ruiter, Jos P.N., Treacy, Eileen P., de Vries, Maaike, Ferdinandusse, Sacha, Bosch, Annet M.
Format: Article
Language:English
Subjects:
Classical Galactosemia
Cohort Studies
Female
Fibroblasts
Fibroblasts - metabolism
Galactose - metabolism
Galactosemias - diagnosis
Galactosemias - genetics
Galactosemias - metabolism
Galactosemias - physiopathology
Galactosephosphates - metabolism
GALT deficiency
Genotype
Homozygote
Humans
Inborn error of metabolism
Infant, Newborn
Intellectual Disability - diagnosis
Male
Movement Disorders - diagnosis
Neonatal Screening
Phenotype
Residual galactose metabolism
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Summary:The high variability in clinical outcome of patients with Classical Galactosemia (CG) is poorly understood and underlines the importance of prognostic biomarkers, which are currently lacking. The aim of this study was to investigate if residual galactose metabolism capacity is associated with clinical and biochemical outcomes in CG patients with varying geno- and phenotypes. Galactose Metabolite Profiling (GMP) was used to determine residual galactose metabolism in fibroblasts of CG patients. The association between the galactose index (GI) defined as the ratio of the measured metabolites [U13C]Gal-1-P/ [13C6]UDP-galactose, and both intellectual and neurological outcome and galactose-1-phosphate (Gal-1-P) levels was investigated. GMP was performed in fibroblasts of 28 patients and 3 control subjects. The GI of the classical phenotype patients (n = 22) was significantly higher than the GI of four variant patients detected by newborn screening (NBS) (p = .002), two homozygous p.Ser135Leu patients (p = .022) and three controls (p = .006). In the classical phenotype patients, 13/18 (72%) had a poor intellectual outcome (IQ 
ISSN:1096-7192
1096-7206
DOI:10.1016/j.ymgme.2020.01.002