ELSEVIER Brain & Development 1995; 17:276-9 Case report An atypical French form of pyruvate carboxylase deficiency Merce Pineda a,* Jaume Campistol a, M. Antonia Vilaseca b, Paz Briones c, Antonia Ribes d, Teresa Temudo a, Marti Pons e, Victoria Cusi f, Marie-Odile Rolland g a Serveis de Neuropediatria, Hospital Universitari Sant Joan de Ddu, Carretera d'Esplugues s / n, 08034 Barcelona, Spain b Serveis de Bioqulmica, Hospital Universitari Sant Joan de Ddu, Barcelona, Spain c CSIC, Consorci Sanitari, Cerdanyola, Barcelona, Spain d Institut de Bioqulmica Cffnica, Cerdanyola, Barcelona, Spain e Serveis de Pediatria, Hospital Universitari Sant Joan de Ddu, Barcelona, Spain f Serveis deAnatomia Patolbgica, Hospital Universitari Sant Joan de Ddu, Barcelona, Spain g Service de Biochimie, Hrpital Debrousse, Lyon, France Received 5 January 1995; accepted 8 April 1995 A further case of pyruvate carboxylase deficiency, French type, with a particular clinical presentation and evolution is described. The initial neonatal symptoms started with respiratory distress, severe metabolic acidosis and a tendency to hypoglycemia. However, the clinical course was not rapidly deteriorating. At the age of 6 months he presented acute neurological symptoms, respiratory difficulty, lactic acidosis and hyperammonemia. Amino and organic acid abnormalities strongly suggested pyruvate carboxylase deficiency, which was confirmed by enzymatic studies in cultured fibroblasts and liver necropsy. Progressive deterioration and bronchopneumonia with cardiac failure and renal insufficiency led to death. Anatomic-pathologic studies revealed periventricular cysts and diffuse hypomyelination. Prenatal diagnosis of a further sibling was performed. The neonatal clinical presentation, biochemical abnormalities, and the presence of periventricular cysts suggested a French phenotype. However, the clinical course was less severe, suggesting a residual enzymatic activity and a possible milder mutation. Keywords: Pyruvate carboxylase deficiency; Lactic acidemia; Inborn errors of metabolism; Prenatal diagnosis; Periventricular cysts 1. INTRODUCTION Pyruvate carboxylase (PC) is a biotin-dependent enzyme of the mitochondrial matrix that catalyzes the carboxylation of pyruvate to oxalacetate. Two clinical forms of PC defi- ciency have been described [1]. The neonatal form, PC type B or French phenotype, presents in the first days of life with severe biotin unresponsive lactic acidosis, hyperammonemia and hypercitrullinemia, leading to death in the first few months of life. It is associated with absent or severely de- creased cross reacting material and almost undetectable en- zymatic activity [2-4]. PC deficiency type A, North American phenotype, has a less severe clinical presentation with important psychomotor delay, and death in infancy or early childhood. Lactic acidemia with ketonemia are the main biochemical features. * Corresponding author. Fax: (34) (3) 280 3626. 0387-7604/95/$09.50 © 1995 Elsevier Science B.V. All rights reserved SSDI 0387-7604(95)00057-7 Cross-reacting material is positive, which results in some residual enzymatic activity that determines the milder clinical and biochemical phenotype [5-8]. The diagnosis of this autosomal-recessively inherited dis- ease is based on metabolite analysis and is confirmed by measuring the enzymatic activity in cultured fibroblasts and liver. Prenatal diagnosis is possible by enzymatic studies in chorionic villi or amniocytes [9,10]. cDNA has been isolated and cloned, and the PC gene localized in the long arm of chromosome 11 [1]. We describe here another case of a French type PC deficiency who presented a particular clinical and biochemi- cal phenotype. 2. CASE REPORT A male infant was the first child of a first degree related couple. Pregnancy was complicated with maternal hyper-