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The 1-¹³ C 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 CO₂ 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.

SUBMITTER: Welsink-Karssies MM

PROVIDER: S-EPMC7317391 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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The 1-<sup>13</sup> C galactose breath test in GALT deficient patients distinguishes NBS detected variant patients but does not predict outcome in classical phenotypes.

Welsink-Karssies Mendy M MM van Harskamp Dewi D Ferdinandusse Sacha S Hollak Carla E M CEM Huidekoper Hidde H HH Janssen Mirian C H MCH Kemper E Marleen EM Langendonk Janneke G JG Rubio-Gozalbo M Estela ME de Vries Maaike C MC Wijburg Frits A FA Schierbeek Henk H Bosch Annet M AM

Journal of inherited metabolic disease 20200122 3

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-<sup>13</sup> C galactose breath t ...[more]

PMID: 31845337

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Project description:Objectives: Fontan-associated liver disease (FALD) is the most common end-organ dysfunction affecting up to 70-80% of the Fontan population. The clinical significance of FALD is incompletely understood and no unambiguous correlation between hepatic function and FALD severity has been established. In this study, we sought to evaluate maximal liver function capacity with liver maximum function capacity test (LiMAx®) in adult Fontan patients. Methods: Thirty-nine adult Fontan patients (median age: 29.4 years [IQR 23.4; 37.4], median follow-up after Fontan operation: 23.9 years [IQR 17.8;26.4]) were analyzed in a cross-sectional observational study using LiMAx® test (Humedics GmbH, Berlin, Germany), laboratory testing, transient elastography (TE) and hepatic ultrasound. The LiMAx® test is based on the metabolism of 13C-methacetin, which is administered intravenously and cleaved by the hepatic cytochrome P4501A2 to paracetamol and 13CO2, which is measured in exhaled air and correlates with maximal liver function capacity. Results: Maximal liver function capacity assessed by LiMAx® test was normal in 28 patients (>315 μg/h*kg) and mildly to moderately impaired in 11 patients (140-314 μg/h*kg), while no patient displayed severe hepatic impairment (<139 μg/kg*h). No correlation was found between maximal liver function capacity and hepatic stiffness by TE (r 2 = -0.151; p = 0.388) or the presence of sonographic abnormalities associated with FALD (r 2 = -0.204, p = 0.24). There was, however, an association between maximal liver function capacity and the laboratory parameters bilirubin (r 2 = -0.333, p = 0.009) and γ-glutamyl transferase (r 2 = -0.367; p = 0.021). No correlation was detected between maximal liver function capacity and the severity of FALD (r 2 = -0.235; p = 0.152). Conclusion: To the best of our knowledge, this is the first study to evaluate maximal liver function capacity using LiMAx® test in Fontan patients, which is a useful complementary diagnostic instrument to assess chronic hepatic injury. Maximal liver function capacity was preserved in most of our adult Fontan patients despite morphologic evidence of FALD. Moreover, maximal liver function capacity does not correlate with the extent of FALD severity evaluated by sonography or laboratory analysis. Thus, the development and progression of FALD in Fontan patients is not a uniform process and diagnostics of chronic hepatic injury during follow-up should encompass various modalities.

Dataset Information

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

Publications

The 1-<sup>13</sup> C galactose breath test in GALT deficient patients distinguishes NBS detected variant patients but does not predict outcome in classical phenotypes.

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Dataset Information

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

Publications

The 1-<sup>13</sup> C galactose breath test in GALT deficient patients distinguishes NBS detected variant patients but does not predict outcome in classical phenotypes.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

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