caa a22 4500 469045302 CHVBK 20180323132822.0 cr unu---uuuuu 170328e19920301xx s 000 0 eng 10.1007/BF01799632 doi (NATIONALLICENCE)springer-10.1007/BF01799632 3-Methylglutaconic aciduria: A marker for as yet unspecified disorders and the relevance of prenatal diagnosis in a ‘new' type (‘type 4') [Elektronische Daten] [D. Chitayat, J. Chemke, K. Gibson, O. Mamer, J. Kronick, J. McGill, B. Rosenblatt, L. Sweetman, C. Scriver] Summary: The Mendelian disorder known as 3-methylgutaconic aciduria (McKusick 250950) gives evidence of allelic and locus heterogeneity. Type 1 has a mild clinical phenotype and confirmed 3-methylgutaconyl-CoA hydratase deficiency; inheritance is autosomal recessive. Other forms have major clinical manifestations and subdivide into X-linked (type 2), a form in Iraqi Jews with optic atrophy (so-called type 3); and untyped (putative autosomal recessive) forms without identified enzyme defects. In the latter, 3-methylglutaconic aciduria may simply be a marker for another metabolic disorder. We describe a male proband with 3-methylglutaconic aciduria designated here as ‘type 4' (autosomal recessive, with severe psychomotor phenotype and cerebellar dysgenesis). He is the offspring of Italian consanguineous parents. Born with congenital malformations, he has been followed for 18 years, showing profound developmental delay and cerebellar dysgenesis. Measures of hydratase activity in cultured fibroblasts from the proband and 11 additional patients (two with type 1 disease, 9 with either type 2 or an unspecified form) revealed deficient enzyme activity in type 1 cases and normal activity in the proband and the other 11 cases. Two of the untyped cases probably have 3-methylglutaconic aciduria of the type described here. Prenatal diagnosis in the form described here may be feasible by analysis of amniotic fluid metabolites in pregnancies at risk if the mother does not entirely remove elevated concentrations. A female sibling of the proband had normal metabolite values in amniotic fluid. Postnatal follow-up confirmed absence of the disease. We give the normal values for amniotic fluid and results on these additional fetuses at risk (none affected). SSIEM and Kluwer Academic Publishers, 1992 Chitayat D. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut Chemke J. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut Gibson K. Kimberly H. Courtwright and Joseph W. Summers Metabolic Disease Center and the Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA aut Mamer O. MRC Gas Chromatography-Mass Spectrometry Unit, McGill University, Montreal, Quebec, Canada aut Kronick J. Department of Pediatrics, University of Western Ontario, London, Ontario, Canada aut McGill J. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut Rosenblatt B. Division of Neurology, Department of Pediatrics, The Montreal Children's Hospital, Montreal, Quebec, Canada aut Sweetman L. Division of Medical Genetics, Children's Hospital, Los Angeles, California, USA aut Scriver C. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/2(1992-03-01), 204-212 0141-8955 15:2<204 1992 15 10545 https://doi.org/10.1007/BF01799632 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF01799632 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Chitayat D. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut NATIONALLICENCE 700 1- Chemke J. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut NATIONALLICENCE 700 1- Gibson K. Kimberly H. Courtwright and Joseph W. Summers Metabolic Disease Center and the Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA aut NATIONALLICENCE 700 1- Mamer O. MRC Gas Chromatography-Mass Spectrometry Unit, McGill University, Montreal, Quebec, Canada aut NATIONALLICENCE 700 1- Kronick J. Department of Pediatrics, University of Western Ontario, London, Ontario, Canada aut NATIONALLICENCE 700 1- McGill J. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut NATIONALLICENCE 700 1- Rosenblatt B. Division of Neurology, Department of Pediatrics, The Montreal Children's Hospital, Montreal, Quebec, Canada aut NATIONALLICENCE 700 1- Sweetman L. Division of Medical Genetics, Children's Hospital, Los Angeles, California, USA aut NATIONALLICENCE 700 1- Scriver C. A-707, De Belle Laboratory for Biochemical Genetics, Division of Medical Genetics, Department of Pediatrics, The Montreal Children's Hospital, 2300 Tupper Street, H3H 1P3, Montreal, Quebec, Canada aut NATIONALLICENCE 773 0- Journal of Inherited Metabolic Disease Kluwer Academic Publishers 15/2(1992-03-01), 204-212 0141-8955 15:2<204 1992 15 10545 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer