TY - JOUR
T1 - The 1-13C galactose breath test in GALT deficient patients distinguishes NBS detected variant patients but does not predict outcome in classical phenotypes
AU - Welsink-Karssies, Mendy M.
AU - van Harskamp, Dewi
AU - Ferdinandusse, Sacha
AU - Hollak, Carla E. M.
AU - Huidekoper, Hidde H.
AU - Janssen, Mirian C. H.
AU - Kemper, E. Marleen
AU - Langendonk, Janneke G.
AU - Rubio-Gozalbo, M. Estela
AU - de Vries, Maaike C.
AU - Wijburg, Frits A.
AU - Schierbeek, Henk
AU - Bosch, Annet M.
N1 - Funding Information: The authors would like to thank Diana Ruffato Resende Campanholi for providing insight into the galactose oxidation calculations used in the study ?Galactose oxidation using 13C in healthy and galactosemic children?. Publisher Copyright: © 2019 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM Copyright: Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/5/1
Y1 - 2020/5/1
N2 - 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- 13C galactose breath test was used to assess whole body galactose oxidation capacity. Participants received a 7 mg/kg oral dose of 1- 13C labelled galactose. The galactose oxidation capacity was determined by calculating the cumulative percentage dose of the administered galactose (CUMPCD) recovered as 13CO 2 in exhaled air. Forty-one CG patients (5–47 years) and four adult controls were included. The median galactose oxidation capacity after 120 minutes (CUMPCDT120) of 34 classical patients (0.29; 0.08–7.51) was significantly lower when compared to two homozygous p.Ser135Leu patients (9.44; 8.66–10.22), one heterozygous p.Ser135Leu patient 18.59, four NBS detected variant patients (13.79; 12.73–14.87) and four controls (9.29; 8.94–10.02). There was a clear correlation between Gal-1-P levels and CUMPCDT120 (P <.0005). In the classical patients, the differences in CUMPCDT120 were small and did not distinguish between patients with poor and normal clinical outcomes. The galactose breath test distinguished classical patients from homo- and heterozygous p.Ser135Leu and NBS detected variant patients, but was not able to predict clinical outcomes in classical patients. Future studies are warranted to enable individualised prognostication and treatment, especially in NBS variants with galactose oxidation capacities in the control range.
AB - 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- 13C galactose breath test was used to assess whole body galactose oxidation capacity. Participants received a 7 mg/kg oral dose of 1- 13C labelled galactose. The galactose oxidation capacity was determined by calculating the cumulative percentage dose of the administered galactose (CUMPCD) recovered as 13CO 2 in exhaled air. Forty-one CG patients (5–47 years) and four adult controls were included. The median galactose oxidation capacity after 120 minutes (CUMPCDT120) of 34 classical patients (0.29; 0.08–7.51) was significantly lower when compared to two homozygous p.Ser135Leu patients (9.44; 8.66–10.22), one heterozygous p.Ser135Leu patient 18.59, four NBS detected variant patients (13.79; 12.73–14.87) and four controls (9.29; 8.94–10.02). There was a clear correlation between Gal-1-P levels and CUMPCDT120 (P <.0005). In the classical patients, the differences in CUMPCDT120 were small and did not distinguish between patients with poor and normal clinical outcomes. The galactose breath test distinguished classical patients from homo- and heterozygous p.Ser135Leu and NBS detected variant patients, but was not able to predict clinical outcomes in classical patients. Future studies are warranted to enable individualised prognostication and treatment, especially in NBS variants with galactose oxidation capacities in the control range.
KW - CO
KW - galactose oxidation
KW - inborn error of metabolism
KW - isotope ratio mass spectrometry
UR - http://www.scopus.com/inward/record.url?scp=85077929324&partnerID=8YFLogxK
U2 - https://doi.org/10.1002/jimd.12207
DO - https://doi.org/10.1002/jimd.12207
M3 - Article
C2 - 31845337
SN - 0141-8955
VL - 43
SP - 507
EP - 517
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 3
ER -