Disease relevance of Multiple Carboxylase Deficiency

• Two patients with biotin-responsive multiple carboxylase deficiency, both presenting with predominant lactic acidosis, are reported [1].
• Six cases of mucopolysaccharidosis, four multiple carboxylase deficiency, three 2-methylacetoacetyl CoA thiolase deficiency, two methymalonic aciduria, one glutaric aciduria type I, one glutaric aciduria type II, one a-oxoglutaric aciduria, and one case of orotic aciduria were detected [2].
• For most previously reported patients, holocarboxylase synthetase deficiency has correlated with the early-onset variant of multiple carboxylase deficiency; conversely, biotinidase deficiency has been characteristic of the late-onset form [3].

High impact information on Multiple Carboxylase Deficiency

• Impaired intestinal absorption of biotin in juvenile multiple carboxylase deficiency [4].
• Deficient biotinidase activity in late-onset multiple carboxylase deficiency [5].
• Using cultured skin fibroblasts, we studied the heterogeneity of inborn errors of leucine metabolism such as isovaleric acidemia (IVA), glutaric aciduria type II (GA II), and multiple carboxylase deficiency (MC) [6].
• Biotin-responsive multiple carboxylase deficiency is an inherited disorder of organic acid metabolism in man in which there are deficiencies of propionyl-coenzyme A (CoA), 3-methylcrotonyl-CoA, and pyruvate carboxylases that can be corrected with large doses of biotin [7].
• Multiple carboxylase deficiency (MCD) is a life-threatening disease characterized by the lack of carboxylase activities because of deficiency of HCS activity [8].

Chemical compound and disease context of Multiple Carboxylase Deficiency

• In biotin-responsive multiple carboxylase deficiency, a characteristic organic aciduria reflects in vivo deficiency of mitochondrial propionyl CoA carboxylase, 3-methylcrotonyl CoA carboxylase, and pyruvate carboxylase [9].
• We report here an impairment of immunoregulatory function, due to defective PGE monocytic production, in a 12-month-old boy with multiple carboxylase deficiency (MCD) [10].
• Children with juvenile-onset multiple carboxylase deficiency lack biotinidase activity (biotinamide amidohydrolase, EC 3.5.1.12) in the liver and other tissues [11].
• This revealed elevated urinary excretion of the characteristics metabolites, 3-hydroxypropionate, 3-hydroxyisovalerate and methylcitrate, suggesting multiple carboxylase deficiency (MCD) [12].
• A definitive diagnosis could be made in 7 of 9 patients studied up to now: 4 patients suffered from biotin-nonresponsive isolated PCC-deficiency, and 3 patients from biotin-responsive multiple carboxylase deficiency caused by deficient biotinidase activity [13].

Biological context of Multiple Carboxylase Deficiency

• Lipid metabolism in biotin-responsive multiple carboxylase deficiency [14].

Anatomical context of Multiple Carboxylase Deficiency

• The concentration of 3-hydroxyisovaleric acid in ten normal amniotic fluid was 4.52 +/- 1.73 mumol/l. The level was elevated eight-fold in the amniotic fluid from a pregnancy resulting in the birth of a child with biotin-responsive multiple carboxylase deficiency [15].

Gene context of Multiple Carboxylase Deficiency

• The recent finding that biotinidase deficiency is the primary biochemical defect in late-onset multiple carboxylase deficiency was stimulated new interest in the inherited disorders of biotin-dependent carboxylases [16].
• OBJECTIVE: Multiple carboxylase deficiency (MCD, MIM:253270) is a common organic aciduria and caused by deficiency of either biotinidase or holocarboxylase synthetase (HLCS; EC 6.3.4.10) [17].
• The modest decrements in ACC activity in normal and infantile-onset cells may be related to the compromised epidermal integrity observed in that form of multiple carboxylase deficiency [9].
• Multiple carboxylase deficiency is characterized by deficient activities of three biotin-dependent enzymes, propionyl coenzyme A carboxylase, pyruvate carboxylase, and beta-methylcrotonyl coenzyme A carboxylase [18].
• The study population consisted of five patients with propionic acidemia (PA), eight with methylmalonic acidemia (MMA; four responsive to vitamin B12), one each with multiple carboxylase deficiency and transcobalamin-II deficiency, and five healthy volunteers [19].

References