No abstract

We describe a similar metabolic pattern of hyperketosis, ketonaciduria, and C6-C12 dicarboxylic aciduria in a patient with the Silver-Russell syndrome and a patient with the Brachmann-de Lange syndrome. Fasting blood levels of beta-hydroxybutyrate and acetoacetate were significantly higher than in age-matched controls, and both patients showed massive urinary excretion of beta-hydroxybutyrate, acetoacetate and C6-C12 dicarboxylic acids.

Various structural defects of collagen type I have been established in 01 and molecular heterogeneity is reflected by clinical variability. We recently reported a cysteine substitution in the C-terminal cyanogen bromide peptide al(1) CB6 of a newborn with lethal 01 arisen by new mutation in one of the al(1) collagen genes (Steinmnn et al., J.Biol.Chem.259:11129, 1984). At that time we speculated, and later confirmed that a cysteine was substituted for a glycine, residue 988 of the helical portion, as a result of a single base change (Cohn et al., in prep.). We now report that in another patient and his mother with mild 01 (Nicholls et al., Brit.Med.J. 288:112, 1984) half of their al(1) chains also contain a cysteine in the crl(1) CB6 peptide as determined by CNBr mapping on 2-dimensional gel electrophoresis in SDS. In contrast to the 1st patient, production, secretion, intracellular degradation, posttranslational modification and helix stability of the collagen were normal. Since the stability of the collagen helix strictly depends on the presence of glycine in every third position, we conclude that in the patient with lethal 01 the cysteine substitution in the glycine position impairs triple-helix formation and stability for sterical reasons, whereas in the two patients with mild 01 cysteine is substituted for an amino acid in the X or Y position of one of the repeating Gly-X-Y triplets. How this latter structural anomaly produces the mild phenotype is unknown at present. INCREASED 6-AND w-OXIDATION OF FATTY ACIDS IN THE SILVER20 RUSSELL SYNDROME PJ willemsl, I Stolte-~ijkstra~, H Schierbeekl, R Bergerl and GPA Smitl Depts of pediatrics1 and Human ~enetics', University of Groningen, Groningen, The NetherlandsWe 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 6-hydroxybutyrate (BHB) and aceto-acetate (AA) and a massive urinary excretion of Cg-CI2 dicarboxylic acids. After 20 hrs ! of fasting BHB in blood was 3.50 and 3.50 mmol/l while AA was 1.02 and I 1.12 mmol/l in the two Silver-Russell dwarfs, respectively. Seven controls of comparable age ( 1 -2 $ yr) had significanly lower blood levels of BHB (mean: 1.68 mmol/l) and AA (mean: 0.63 mmol/l). GC-MS analysis of urine organic acids of both Silver-Russell patients showed a very similar pattern with a massive excretion of BHB (