Dataset Information

Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.

ABSTRACT: (1) Background: Deficiencies of mitochondrial fatty acid oxidation (FAO) define a subgroup of inborn errors of metabolism, with medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) being two of the most common. Hypoketotic hypoglycemia is a feared clinical complication and the treatment focuses on avoiding hypoglycemia. In contrast, carnitine uptake deficiency (CUD) is treated as a mild disease without significant effects on FAO. Impaired FAO has experimentally been shown to impair glucagon secretion. Glucagon is an important glucose-mobilizing hormone. If and how glucagon is affected in patients with VLCAD or MCAD remains unknown. (2) Methods: A cross-sectional study was performed with plasma hormone concentrations quantified after four hours of fasting. Patients with VLCAD (n = 10), MCAD (n = 7) and CUD (n = 6) were included. (3) Results: The groups were similar in age, sex, weight, and height. The glucagon and insulin levels were significantly lower in the VLCAD group compared to the CUD group (p < 0.05, respectively). The patients with CUD had glucagon concentrations similar to the normative data. No significant differences were seen in GLP-1, glicentin, glucose, amino acids, or NEFAs. (4) Conclusions: Low fasting concentrations of glucagon are present in patients with VLCAD and cannot be explained by altered stimuli in plasma.

SUBMITTER: Stenlid R

PROVIDER: S-EPMC10386500 | biostudies-literature | 2023 Jun

REPOSITORIES: biostudies-literature

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Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.

Stenlid Rasmus R Manell Hannes H Seth Rikard R Cerenius Sara Y SY Chowdhury Azazul A Roa Cortés Camilla C Nyqvist Isabelle I Lundqvist Thomas T Halldin Maria M Bergsten Peter P

Metabolites 20230622 7

(1) Background: Deficiencies of mitochondrial fatty acid oxidation (FAO) define a subgroup of inborn errors of metabolism, with medium-chain acyl-CoA dehydrogenase deficiency (MCAD) and very long-chain acyl-CoA dehydrogenase deficiency (VLCAD) being two of the most common. Hypoketotic hypoglycemia is a feared clinical complication and the treatment focuses on avoiding hypoglycemia. In contrast, carnitine uptake deficiency (CUD) is treated as a mild disease without significant effects on FAO. Imp ...[more]

PMID: 37512487

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Project description:BackgroundVery-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency (VLCADD) is diagnosed in the US through newborn screening (NBS). NBS often unequivocally identifies affected individuals, but a growing number of variant patterns can represent mild disease or heterozygous carriers.AimsTo evaluate the validity of standard diagnostic procedures for VLCADD by using functional in vitro tools.MethodsWe retrospectively investigated 13 patient samples referred to our laboratory because of a suspicion of VLCADD but with some uncertainty to the diagnosis. All 13 patients were suspected of having VLCADD either because of abnormal NBS or suggestive clinical findings. ACADVL genomic DNA sequencing data were available for twelve of them. Ten of the patients had an abnormal NBS suggestive of VLCADD, with three samples showing equivocal results. Three exhibited suggestive clinical findings and blood acylcarnitine profile (two of them had a normal NBS and the third one was unscreened). Assay of VLCAD activity and immunoblotting or immunohistologic staining for VLCAD were performed on fibroblasts. Prokaryotic mutagenesis and expression studies were performed for nine uncharacterized ACADVL missense mutations.ResultsVLCAD activity was abnormal in fibroblast cells from 9 patients (8 identified through abnormal NBS, 1 through clinical symptoms). For these 9 patients, immunoblotting/staining showed the variable presence of VLCAD; all but one had two mutated alleles. Two patients with equivocal NBS results (and a heterozygous genotype) and the two patients with normal NBS exhibited normal VLCAD activity and normal VLCAD protein on immunoblotting/staining thus ruling out VLCAD deficiency. Nine pathogenic missense mutations were characterized with prokaryotic expression studies and showed a decrease in enzyme activity and variable stability of VLCAD antigen.ConclusionsThese results emphasize the importance of functional investigation of abnormal NBS or clinical testing suggestive but not diagnostic of VLCADD. A larger prospective study is necessary to better define the clinical and metabolic ramifications of the defects identified in such patients.

Dataset Information

Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.

Publications

Low Fasting Concentrations of Glucagon in Patients with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency.

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