The 1‐¹³C galactose breath test in GALT deficient patients distinguishes NBS detected variant patients but does not predict outcome in classical phenotypes

Abstract

Classical galactosemia (CG) patients frequently develop long-term complications despite early dietary treatment. The highly variable clinical outcome is poorly understood and a lack of prognostic biomarkers hampers individual prognostication and treatment. The aim of this study was to investigate the association between residual galactose oxidation capacity and clinical and biochemical outcomes in CG patients with varying geno-and phenotypes. The noninvasive 1-13 C galactose breath test was used to assess whole body galactose oxidation capacity.Participants received a 7 mg/kg oral dose of 1-13 C labelled galactose. The galactose oxidation capacity was determined by calculating the cumulative percentage dose of the administered galactose (CUMPCD) recovered as 13 CO 2 in exhaled air.Abbreviations: CG, classical galactosemia; CUMPCD, cumulative percentage of the administered dose recovered; Gal-1-P, galactose-1-phosphate; GALT, galactose-1-phosphate uridyltransferase; IQ, intelligence quotient; MD, movement disorder.

Multi‐omics in classical galactosemia: Evidence for the involvement of multiple metabolic pathways

“…In our cohort, the most recently measured Gal‐1P levels allowed us to discriminate between classical patients (severe GALT deficiency) and variant patients identified by newborn screening with higher residual GALT activity and better outcomes, but not between classical patients with a poor versus normal clinical outcome. Furthermore, differences in outcome in classical patients with a severe GALT deficiency in our cohort did not correlate with other parameters including in vivo galactose oxidation, in vitro galactose oxidation, and IgG galactosylation 2,6,7 …”

“…Furthermore, differences in outcome in classical patients with a severe GALT deficiency in our cohort did not correlate with other parameters including in vivo galactose oxidation, in vitro galactose oxidation, and IgG galactosylation. 2,6,7 Major technological advances in metabolomics have resulted in the ability to analyze vast numbers of metabolites in patients' cells and body fluids simultaneously. Metabolite analysis of small molecules (metabolomics) and complex lipids (lipidomics) may result in better understanding of the underlying disease mechanisms and improve patient prognostication with validated biomarkers.…”