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

Autor: Hidde H. Huidekoper, Henk Schierbeek, M. Estela Rubio-Gozalbo, Frits A. Wijburg, Carla E. M. Hollak, Mendy M. Welsink-Karssies, Sacha Ferdinandusse, Janneke G. Langendonk, E. Marleen Kemper, Maaike de Vries, Mirian C. H. Janssen, Dewi van Harskamp, Annet M. Bosch
Přispěvatelé: Graduate School, AGEM - Inborn errors of metabolism, AGEM - Digestive immunity, AGEM - Endocrinology, metabolism and nutrition, APH - Methodology, APH - Quality of Care, Amsterdam Reproduction & Development (AR&D), Laboratory Genetic Metabolic Diseases, Endocrinology, Pharmacy, Medical Microbiology and Infection Prevention, Paediatric Metabolic Diseases, General Paediatrics, RS: GROW - R4 - Reproductive and Perinatal Medicine, Kindergeneeskunde, MUMC+: MA Medische Staf Kindergeneeskunde (9), Pediatrics, Internal Medicine
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Oral dose
Male
Future studies
13CO2
Gastroenterology
chemistry.chemical_compound
isotope ratio mass spectrometry
Child
Genetics (clinical)
medicine.diagnostic_test
Galactosemia
Galactosephosphates
Homozygote
Metabolic Disorders Radboud Institute for Molecular Life Sciences [Radboudumc 6]
Middle Aged
Phenotype
CO
galactose oxidation
Breath Tests
Child
Preschool
Original Article
Female
Oxidation-Reduction
Adult
Galactosemias
medicine.medical_specialty
Adolescent
Genotype
oxidation
C-13
Young Adult
All institutes and research themes of the Radboud University Medical Center
Internal medicine
Genetics
medicine
inborn error of metabolism
Humans
UTP-Hexose-1-Phosphate Uridylyltransferase
Breath test
business.industry
Siblings
Galactose
Original Articles
medicine.disease
chemistry
Dietary treatment
(co2)-c-13
Inborn error of metabolism
Case-Control Studies
business
Zdroj: Journal of inherited metabolic disease, 43(3), 507-517. Springer Netherlands
Journal of Inherited Metabolic Disease, 43(3), 507-517. Wiley
Journal of Inherited Metabolic Disease, 43, 507-517
Journal of Inherited Metabolic Disease
Journal of Inherited Metabolic Disease, 43, 3, pp. 507-517
Journal of Inherited Metabolic Disease, 43(3), 507-517. Springer Netherlands
ISSN: 1573-2665
0141-8955
Popis: 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 13CO2 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.
Databáze: OpenAIRE
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