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Summary: Zellweger syndrome (ZS), or cerebrohepatorenal syndrome, was the first described peroxisomal biogenesis disorder. It represents the most severe phenotype, and some of its multiple congenital anomalies can manifest prenatally. Fetal hypokinesia, renal hyperechogenicity, and cerebral ventricular enlargement are the most common reported fetal features. Single and/or late detectable manifestations account for most of the difficulties of prenatal diagnosis, as well as the limitations of ultrasonography itself. Prenatal diagnosis, however, can be achieved through (1) assays of concentrations of peroxisomal metabolites (very-long-chain fatty acids, bile acids, intermediates, plasmalogens), (2) activities of peroxisomal enzymes (dihydroacetone-phosphate acyltransferase), or (3) molecular screening techniques, if available. We report on the contribution of MR imaging to the diagnosis of ZS in 2 unrelated fetuses. MR imaging was performed in the third trimester because of cerebral ventricular enlargement diagnosed on routine sonography examinations. In both cases, MR imaging revealed ZS-characteristic abnormal cortical gyral patterns, impaired myelination, and cerebral periventricular pseudocysts. In addition, MR imaging revealed renal microcysts and hepatosplenomegaly in one case. The high level of resolution of MR imaging, which allows analysis of cerebral gyration and myelination, facilitates the prenatal diagnosis of complex polymalformative syndromes such as ZS.

Ornithine transcarbamylase (OTC) deficiency is an inborn error of urea cycle metabolism, responsible for lethal hyperammonemia in males and for severe symptoms in at least 20% of heterozygous females. The authors provide here additional data on the informativity of the protein loading test (PLT) for the detection of heterozygotes. They show that the risk of being a carrier for the mother of an affected boy falls from 2/3 a priori to only 1/8 if her PLT is negative. The risk for the mother of heterozygote girl falls from 1/2 a priori to 1/16 if her PLT is negative.

Nineteen children with defects of the mitochondrial respiratory chain are described. First symptoms appeared during the first two years of their lives. Four types of clinical pictures were identified: 1/neonatal hypotonia. 2/cardiomyopathy. 3/progressive neurological deterioration. 4/multisystem disease. A study of pyruvate and fatty acids metabolism and a skeletal muscle biopsy were performed in all cases. Elevation of beta-hydroxybutyrate/acetoacetate and lactate were the most frequent biochemical abnormalities. Muscular biopsy in light microscopy showed in most cases abnormal lipid storage.

Ornithine transcarbamylase (OTC) deficiency is a frequent X linked disorder of the urea cycle which is responsible for lethal neonatal hyperammonaemia in males and for various clinical symptoms in heterozygous females. In order to improve the efficiency of our screening for mutant genotypes, we focused on molecular domains of functional or structural importance in the OTC gene, namely the carbamyl phosphate binding domain (encoded by the third exon) and the MspI restriction sites (CCGG) of the coding sequence (located in exons 2 and 7 respectively), as they contain mutation hot spots (CpG doublets). Using this procedure, we were able to identify three new mutant genotypes in OTC deficient children including one nonsense mutation (E 87 K, G 50 ter, G 162 R). Since genetic counselling for OTC deficiency is frequently difficult, molecular screening directed towards specific sites of the coding sequence could allow rapid detection of mutant genotypes and help solve diagnostic problems, especially when carrier status cannot be clarified easily.