INCREASED β- AND ω-OXIDATION OF FATTY ACIDS IN THE SILVER RUSSELL SYNDROME

Abstract

We found evidence for an increased oxidation of fatty acids in two Silver-Russell patients (dwarfism of prenatal onset, typical craniofacial appearance and dystrophy).Fasting studies showed elevated blood and urine levels of β-hydroxybutyrate (BHB) and aceto-acetate (AA) and a massive urinary excretion of C6-C12 dicarboxylic acids. After 20 hrs of fasting BHB in blood was 3.50 and 3.50 mmol/1 while AA was 1.02 and 1.12 mmol/1 in the two Silver-Russell dwarfs, respectively. Seven controls of comparable age (1-2½ yr) had significanly lower blood levels of BHB (mean: 1.68 mmol/l) and AA (mean: 0.63 mmol/1). GC-MS analysis of urine organic acids of both Silver-Russell patients showed a very similar pattern with a massive excretion of BHB (<10 mmol/1) and C6-C12 dicarboxylic acids (adipic acid, suberic acid, sebacic acid, C12-dicarboxylic acid, cis/trans unsaturated suberic acid and sebacic acid, cis unsaturated 3-OH-derivates of sebacic acid and C12dicarboxylic acid). In contrast controls had a low excretion of BHB (<1 mmol/l), while C6-C12 dicarboxylic acids were present in very small amounts or not detectable. The combination of both an activated β-oxidation resulting in high blood and urine levels of BHB and AA, and an activated ω-oxidation resulting in a massive urinary excretion of dicarboxylic acids is very typical.We suggest that this increased oxidation of fatty acids is a distinct feature in the Silver-Russell syndrome and might provide an explanation for the dystrophy which is so characteristic.