Abstract
Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an increasingly recognized defect of mitochondrial fatty acid beta-oxidation manifesting with episodes of metabolic decompensation or isolated recurrent myoglobinuria. In this report the clinical, biochemical, and molecular studies in a series of five patients (four Italian and one Spanish) with this disorder are discussed. Biochemical studies included the determination of fibroblast substrate oxidation rates and enzyme activity and Western blot analysis of VLCAD protein. Molecular analysis was performed by sequencing the VLCAD gene from the genomic DNA. Clinical features were within the spectrum previously reported. Four patients presented in infancy or childhood with episodes of severe metabolic decompensation and dicarboxylic aciduria. Two exhibited cardiomyopathy. The fifth patient presented with isolated recurrent rhabdomyolysis, with no cardiomyopathy or dicarboxylic aciduria. In all patients a significant loss of VLCAD activity associated with a marked reduction of VLCAD protein levels occurred. Molecular analysis disclosed one novel missense mutation (Cys437Tyr) and four previously reported mutations, including two missense substitutions (Phe418Leu and Arg419Trp), a single amino acid deletion (Lys258del), and one splice site mutation (IVS8-C-2), which was present in all four Italian patients. All patients exhibited compound heterozygosity. The phenotypic variability and the high genotypic heterogeneity of this hereditary metabolic disorder is reported. (C) 2000 by Elsevier Science Inc.
| Original language | English |
|---|---|
| Pages (from-to) | 98-105 |
| Number of pages | 8 |
| Journal | Pediatric Neurology |
| Volume | 22 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Feb 2000 |
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ASJC Scopus subject areas
- Clinical Neurology
- Pediatrics, Perinatology, and Child Health
- Developmental Neuroscience
- Neurology
Cite this
Clinical and molecular heterogeneity in very-long-chain acyl-coenzyme A dehydrogenase deficiency. / Pons, Roser; Cavadini, Patrizia; Baratta, Silvia; Invernizzi, Federica; Lamantea, Eleonora; Garavaglia, Barbara; Taroni, Franco.
In: Pediatric Neurology, Vol. 22, No. 2, 02.2000, p. 98-105.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Clinical and molecular heterogeneity in very-long-chain acyl-coenzyme A dehydrogenase deficiency
AU - Pons, Roser
AU - Cavadini, Patrizia
AU - Baratta, Silvia
AU - Invernizzi, Federica
AU - Lamantea, Eleonora
AU - Garavaglia, Barbara
AU - Taroni, Franco
PY - 2000/2
Y1 - 2000/2
N2 - Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an increasingly recognized defect of mitochondrial fatty acid beta-oxidation manifesting with episodes of metabolic decompensation or isolated recurrent myoglobinuria. In this report the clinical, biochemical, and molecular studies in a series of five patients (four Italian and one Spanish) with this disorder are discussed. Biochemical studies included the determination of fibroblast substrate oxidation rates and enzyme activity and Western blot analysis of VLCAD protein. Molecular analysis was performed by sequencing the VLCAD gene from the genomic DNA. Clinical features were within the spectrum previously reported. Four patients presented in infancy or childhood with episodes of severe metabolic decompensation and dicarboxylic aciduria. Two exhibited cardiomyopathy. The fifth patient presented with isolated recurrent rhabdomyolysis, with no cardiomyopathy or dicarboxylic aciduria. In all patients a significant loss of VLCAD activity associated with a marked reduction of VLCAD protein levels occurred. Molecular analysis disclosed one novel missense mutation (Cys437Tyr) and four previously reported mutations, including two missense substitutions (Phe418Leu and Arg419Trp), a single amino acid deletion (Lys258del), and one splice site mutation (IVS8-C-2), which was present in all four Italian patients. All patients exhibited compound heterozygosity. The phenotypic variability and the high genotypic heterogeneity of this hereditary metabolic disorder is reported. (C) 2000 by Elsevier Science Inc.
AB - Very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency is an increasingly recognized defect of mitochondrial fatty acid beta-oxidation manifesting with episodes of metabolic decompensation or isolated recurrent myoglobinuria. In this report the clinical, biochemical, and molecular studies in a series of five patients (four Italian and one Spanish) with this disorder are discussed. Biochemical studies included the determination of fibroblast substrate oxidation rates and enzyme activity and Western blot analysis of VLCAD protein. Molecular analysis was performed by sequencing the VLCAD gene from the genomic DNA. Clinical features were within the spectrum previously reported. Four patients presented in infancy or childhood with episodes of severe metabolic decompensation and dicarboxylic aciduria. Two exhibited cardiomyopathy. The fifth patient presented with isolated recurrent rhabdomyolysis, with no cardiomyopathy or dicarboxylic aciduria. In all patients a significant loss of VLCAD activity associated with a marked reduction of VLCAD protein levels occurred. Molecular analysis disclosed one novel missense mutation (Cys437Tyr) and four previously reported mutations, including two missense substitutions (Phe418Leu and Arg419Trp), a single amino acid deletion (Lys258del), and one splice site mutation (IVS8-C-2), which was present in all four Italian patients. All patients exhibited compound heterozygosity. The phenotypic variability and the high genotypic heterogeneity of this hereditary metabolic disorder is reported. (C) 2000 by Elsevier Science Inc.
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UR - http://www.scopus.com/inward/citedby.url?scp=0033968629&partnerID=8YFLogxK
U2 - 10.1016/S0887-8994(99)00132-0
DO - 10.1016/S0887-8994(99)00132-0
M3 - Article
C2 - 10738914
AN - SCOPUS:0033968629
VL - 22
SP - 98
EP - 105
JO - Pediatric Neurology
JF - Pediatric Neurology
SN - 0887-8994
IS - 2
ER -