A symptom-free woman gave birth to a girl with a low carnitine level on newborn screening. The baby was unaffected, but the mother had biochemical abnormalities and mutations characteristic of the cblC defect of vitamin B(12) metabolism (late-onset form). This patient with cblC was detected through her infant's newborn screening.

The final step in the conversion of vitamin B(12) into coenzyme B(12) (adenosylcobalamin, AdoCbl) is catalyzed by ATP:cob(I)alamin adenosyltransferase (ATR). Prior studies identified the human ATR and showed that defects in its encoding gene underlie cblB methylmalonic aciduria. Here two common polymorphic variants of the ATR that are found in normal individuals are expressed in Escherichia col...

Two human subjects were given separate oral doses of sodium [2H6]isobutyrate and [methyl-2H3]thymine and the labelling patterns of urinary metabolites were determined. Ingestion of deuterated isobutyrate resulted in the excretion of 2H5-labelled S-3-hydroxyisobutyric acid, formed on the direct catabolic pathway, and of S- and R-[2H4]-3-hydroxyisobutyric acids, formed by the reduction of S- and ...

Combined methylmalonic acidemia (MMA) and homocysteinemia are a group of autosomal recessive disorders caused by inborn errors of cobalamin metabolism, including CblC, D, F, and J, with cblC being the most common subtype. The clinical manifestations of combined MMA and homocysteinemia vary, but typically include neurologic, developmental and hematologic abnormalities.We report 4 children with c...

The separation of organic acids and their elution from silicic acid columns and their quantitative measurement by color change of buffered indicator, a technique mechanized by Kesner and Muntwyler, are applicable to the study of biological materials. As little as 25 g of acid can be measured. Elution times and color yield in terms of peak areas obtained with the commercial apparatus are given f...

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pat...

Defects in two subunits of succinate-CoA ligase encoded by the genes SUCLG1 and SUCLA2 have been identified in mitochondrial DNA (mtDNA) depletion syndromes. Patients generally present with encephalomyopathy and mild methylmalonic acidemia (MMA), however mutations in SUCLG1 normally appear to result in a more severe clinical phenotype. In this report, we describe a patient with fatal infantile ...

Methylmalonic acidemias consist of a group of inherited neurometabolic disorders caused by deficiency of methylmalonyl-CoA mutase activity clinically and biochemically characterized by neurological dysfunction, methylmalonic acid (MMA) accumulation, mitochondrial failure and increased reactive species production. Although previous studies have suggested that nitric oxide (NO) plays a role in th...

BACKGROUND Liver transplantation for inherited metabolic disorders aims to save the patient's life when the disorder is expected to progress to organ failure, and to cure the underlying metabolic defect. METHODS We retrospectively analyzed 146 pediatric liver transplants (28 metabolic; 118 non-metabolic) performed between 1986 and 2000. RESULTS Twenty-eight transplants were performed in 24 ...

Methylmalonic acid (MMA) is a biomarker for vitamin B12 deficiency. This application note describes a fast, simple, and sensitive method to detect MMA in plasma that uses a zwitterionic hydrophilic interaction chromatography (ZIC®-HILIC) column with LC-MS or LC-MS/MS. Introduction Methylmalonic acid (MMA) levels in serum, plasma and urine are used to monitor cobalamin (vitamin B12) deficiency1 ...