malonyl-coenzyme-a and Acidosis

Malonyl-CoA decarboxylase deficiency is an extremely rare autosomal recessive inborn error of fatty acid metabolism. It usually follows a severe disease course and presents poor prognosis without treatment. Here, we report an affected female juvenile with a mild clinical and biochemical phenotype who mainly featured poor schooling without cardiomyopathy and metabolic acidosis. She was suspected of malonyl-CoA decarboxylase deficiency due to a 57-kb deletion in 16q23.3 encompassing the MLCYD gene revealed by chromosome microarray. Malonyl-CoA decarboxylase deficiency was then confirmed by acylcarnitine analysis and organic acid analysis. Real-time PCR analysis of the patient revealed the first three exon deletion of the MLYCD gene, which was maternally inherited. DNA sequencing of the MLYCD gene of the patient identified a novel heterozygous mutation (c.911G>A, p.G304E) in exon 4 that was paternally inherited. The patient urine malonic acid dissolved and had a better school record in 6 month after initiation of fat-limited diet. At 1 year post treatment, the blood malonylcarnitine level decreased remarkably. Our result expands the phenotype of malonyl-CoA decarboxylase deficiency and suggests attentions should be paid to the mild form of disorders, for example, malonyl-CoA decarboxylase deficiency, which usually present a severe disease course.

Topics: Acidosis; Adolescent; Base Sequence; Carboxy-Lyases; Cardiomyopathies; Child; Chromosomes; Exons; Female; Humans; Malonates; Malonyl Coenzyme A; Metabolism, Inborn Errors; Methylmalonic Acid; Microarray Analysis; Sequence Deletion

Methyl malonic academia (MMA) is characterized by abnormal accumulation of methyl malonic acid in body fluids. Patients usually have a variety of clinical symptoms including recurrent vomiting, metabolic acidosis, developmental delay, seizure, or death. However, a few cases where the patients have no symptom are also reported. Here, we conducted clinical, biochemical, and molecular analysis of eight Chinese patients identified through newborn screening between 2003 and 2013. All the patients had significantly higher blood propionylcarnitine (C3) concentrations, ratio of propionylcarnitine/acetylcarnitine (C3/C2); and their urine methyl malonic acid and methylcitric acid (MCA) excretions were remarkably higher than normal at diagnosis and during follow-ups. In addition, five different known mutations were identified in seven of the eight patients in either MUT or MMACHC. All these mutations were expected to produce defective proteins that would result in decreased or even total loss of methyl malonyl-CoA mutase activity. However, normal outcomes were found in all patients in physical growth, intellectual performance and cerebral MRI analysis at diagnosis (range, 14-53 days) and during follow-ups (range, 1.8-10 years). Our study is the first report of Chinese MMA patients with increased secretion of methyl malonic acid and molecular defects in MUT or MMACHC yet remain asymptomatic.

Topics: Acetylcarnitine; Acidosis; Asian People; Asymptomatic Diseases; Carboxy-Lyases; Carnitine; Carrier Proteins; Child; Citrates; Female; Gene Expression; Humans; Infant; Infant, Newborn; Male; Malonates; Malonyl Coenzyme A; Metabolism, Inborn Errors; Methylmalonic Acid; Methylmalonyl-CoA Mutase; Mutation; Neonatal Screening; Oxidoreductases

A new case of mitochondrial malonyl coenzyme A decarboxylase deficiency is described. The patient presented with an initial episode of metabolic acidosis, seizures, hypoglycemia, and cardiac failure at 2 months of age which slowly resolved. Subsequent evaluations at 4 years of age for developmental delay revealed a prominent elevation of malonic acid in urine. Malonyl carnitine was also elevated. The activity of Malonyl CoA decarboxylase in cultured fibroblasts was 7% of normal.. Malonyl CoA decarboxylase deficiency may result in inhibition of fatty acid oxidation, which may account for the cardiomyopathy.

Topics: Acidosis; Carboxy-Lyases; Cardiomyopathies; Developmental Disabilities; Humans; Infant; Lipid Metabolism, Inborn Errors; Male; Malonyl Coenzyme A; Mitochondrial Myopathies

We have examined the roles of liver glycogen and malonyl coenzyme A (CoA) in determining the degree of postexercise ketosis in endurance-trained and nontrained rats. Three groups of rats were run on a treadmill for 90 min: trained (2 h/day, 6 wk) and food restricted to 5.5 g/100 g body wt the night before the 90-min exercise bout (group 1), nontrained fed ad libitum (group 2), and nontrained food restricted (same as trained) (group 3). Liver glycogen was 34 +/- 5, 24 +/- 2, and 7 +/- 2 mg/g in groups 1, 2, and 3, respectively, at the end of exercise. At the end of exercise and during the postexercise period the blood 3-hydroxybutyrate concentration in group 3 was significantly higher than in groups 1 or 2. No difference was observed between groups 1 and 2 in blood 3-hydroxybutyrate. Hepatic malonyl CoA was decreased to the same extent in all rats during exercise but remained depressed only in the glycogen-depleted group 3 rats in the postexercise period. These data suggest that the differences in degree of ketonemia in the postexercise period (but not during exercise) were due to lower hepatic malonyl CoA in group 3 rats.

Topics: 3-Hydroxybutyric Acid; Acidosis; Animals; Carnitine; Cyclic AMP; Hydroxybutyrates; Ketosis; Liver; Liver Glycogen; Male; Malonyl Coenzyme A; Physical Conditioning, Animal; Physical Endurance; Physical Exertion; Rats; Rats, Inbred Strains