Studies in Inherited Metabolic Disease

With improved control of most environmental causes of disease, genetic illness has assumed a primary importance in the causation of handicap and mortality in all age groups. At present, effective therapy is available for relatively few genetic conditions and prenatal diagnosis is an important option for couples at high risk. The task of providing prenatal diagnosis for these couples requires a team approach between clinicians and scientists, and is complicated by the large number of diverse conditions and by the rapid developments in the field, both obstetric in relation to imaging and tissue sampling methods and genetic in relation to techniques for analysis. Against this background, the aim of the Symposium was to provide an overview of the current status of prenatal and perinatal diagnosis of inborn errors of metabolism. The format consisted of the usual mixture of specific invited overviews and free communications in either oral or poster form. The invited overviews, as can be seen from this publication, covered a wide range, from accepted methods for neonatal diagnosis and screening to newer techniques for prenatal diagnosis and likely future developments with respect to gene therapy. Similarly, the oral com­ munications included reviews of experience with biochemical analysis of chorionic villus sampling from major centres, more specific examples of progress towards the basic defect in Batten's disease and Canavan's disease, and prospects for effective therapy in Menkes' disease and a lipid myopathy.

Contenu

Preface.- Perspectives Family influences on A. E. Garrod's thinking.- The salience of Garrod's 'molecular groupings' and 'inborn factors in disease'.- Prenatal and perinatal diagnosis.- Clinical approach to inherited metabolic diseases in the neonatal period: a 20-year survey.- Acute metabolic encephalopathy: a review of causes, mechanisms and treatment.- A clinician's view of the mass screening of the newborn for inherited diseases: current practice and future considerations.- A clinical biochemist's view of the investigation of suspected inherited metabolic disease.- Genetic aspects of prenatal diagnosis.- Obstetric aspects of prenatal diagnostic methods.- Chorionic villus sampling: diagnostic uses and limitations of enzyme assays.- Prenatal and perinatal diagnosis of peroxisomal disorders.- Prenatal diagnosis and prevention of inherited abnormalities of collagen.- Prenatal diagnosis of Duchenne muscular dystrophy: a three-year experience in a rapidly evolving field.- Prospects for gene therapy now and in the future.- Prenatal diagnosis of disorders of galactose metabolism.- Prenatal and postnatal diagnosis of Menkes disease, an inherited disorder of copper metabolism.- Disorders of mitochondrial ?-oxidation: prenatal and early postnatal diagnosis and their relevance to Reye's syndrome and sudden infant death.- Gene mapping of mineral metabolic disorders.- Short Communications.- Preface and Free Communications.- Fifteen years of prenatal diagnosis of inherited metabolic diseases: the Lyon experience.- A survey on prenatal diagnosis of inherited metabolic diseases in Japan.- Prenatal diagnosis of inherited metabolic disease by chorionic villus analysis: the Edinburgh experience.- Prenatal diagnosis of inherited metabolic disorders by stable isotope dilution GC-MS analysis of metabolites in amniotic fluid: review of four years' experience.- Prenatal diagnosis of propionic and methylmalonic acidaemia by stable isotope dilution analysis of amniotic fluid.- Successful first trimester diagnosis in a pregnancy at risk for propionic acidaemia.- First trimester prenatal exclusion of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type 1).- Early prenatal diagnosis in two pregnancies at risk for glutaryl-CoA dehydrogenase deficiency.- First trimester prenatal diagnosis of 3-hydroxy-3-methylglutaric aciduria.- Enzymatic prenatal diagnosis of primary hyperoxaluria type 1: potential and limitations.- First trimester diagnosis of glycogen storage disease type II and type III.- First trimester prenatal diagnosis of glycogen storage disease type III.- Prenatal diagnosis of atypical phenylketonuria.- First trimester prenatal diagnosis of Wolman disease.- Prenatal diagnosis of Zeliweger syndrome by direct visualization of peroxisomes in chorionic villus fibroblasts by immunofluorescence microscopy.- Prenatal diagnosis of cystic fibrosis: experience of two complementary methods.- Prenatal diagnosis of cystic fibrosis using closely linked DNA probes.- Plasma amino acids during the first 24 hours of life: feasibility of early diagnosis in the newborn at risk of amino acid disorders.- Perinatal diagnosis of type 1c glycogen storage disease.- A 'blood spot' androstenedione radioimmunoassay able to detect congenital adrenal hyperplasia.- Generalized dicarboxylic aciduria: a common finding in neonates.- Comparison of urinary acylglycines and acylcarnitines as diagnostic markers of mediumchain acyl-CoA dehydrogenase deficiency.- Aspartoacylase deficiency: the enzyme defect in Canavan disease.- Iatrogenic skin lesions in phenylketonuric children due to a low tyrosine intake.- Primapterinuria: a new variant of atypical phenylketonuria.- Tyrosinaemia type I: orthotopic liver transplantation as the only definitive answer to a metabolic as well as an oncological problem.- Lens hexitols and cataract formation during lactation in a woman heterozygote for galactosaernia.- A method for the diagnosis of glycogen storage disease type Ib using polymorphonuclear leukocytes.- Familial NADH: Q1 oxidoreductase (complex 1) deficiency: variable expression and possible treatment.- Mitochondrial myopathies: multiple enzyme defects in the respiratory chain.- Familial mitochondrial complex I deficiency with an abnormal mitochondrial encoded protein.- Peroxisomal enzyme deficiency in X-linked dominant Conradi-Hünermann syndrome.- The heterogeneity of Leber's congenital amaurosis.- Hurler-Scheie phenotype associated with consanguinity.- Detection of Fabry's disease carriers by enzyme assay of hair roots.- Immunohistochemical demonstration of GM2-ganglioside in the central nervous system of a 19-week-old fetus of Tay-Sachs disease.- Visualization of the sugar moiety in lymphoid cell lines from Fabry's disease by lectin binding.- Identification of intact dolichol-linked oligosaccharides in the brains of patients with ceroidlipofuscinosis (Batten's disease).- Study of pathogenesis in twicher mouse, an enzymatically authentic model of human Krabbe's disease.- Nuclear magnetic resonance brain study in a case of Wilson disease.- Vitamin C treatment in Menkes' disease: failure to affect biochemical and clinical parameters.- Copper histidinate therapy in Menkes' disease: prevention of progressive neurodegeneration.