Biotin-responsive multiple carboxylase deficiency of infantile onset

Abstract

B I O T I N R E S P O N S I V E C A R B O X Y E A S E D E F I C I E N C Y is being identified in a number of patients presenting with a characteristic pattern of lactic acidosis and accumulation of other organic acids. The increased urinary excretion of lactic acid, 3-OH propionic acid, methylcitric acid, 3-methylcrotonylglycine, and 3-OH isovaleric acid is consistent with deficient in vivo activity of at least three biotin-dependent carboxylases: pyruvate carboxylase (EC 6.4.111), propionyl-CoA carboxylase (EC 6.4.1.3), and 3-methylcrotonyl-CoA carboxylase (EC 6.4.1.4). These chemical findings can occur in children with quite disparate clinical courses. Some patients have variable symptoms beginning in the newborn period. 1 ' In addition, there is a more complex syndrome of infantile onset with ataxia, keratoconjunctivitis, al0pecia, and immunodeficiency? -'~ Herein we report our initial biochemical studies of a patient with the infantile-onset form, including studies of biotin levels in physiologic fluids.