Utilize este identificador para referenciar este registo: http://hdl.handle.net/10400.18/1172
Título: 3-Methylcrotonyl CoA Carboxylase Deficiency: Disorder or Just a Biochemical Phenotype?
Autor: Fonseca, Helena
Bueno, Maria
Sousa, Carmen
Marcão, Ana
Lopes, Lurdes
Rocha, Hugo
Vilarinho, Laura
Palavras-chave: 3-Methylcrotonyl-CoA Carboxylase Deficiency
Disorder of Leucine Metabolism
Doenças Genéticas
Data: Nov-2012
Editora: Instituto Nacional de Saúde Doutor Ricardo Jorge, IP
Resumo: Introduction: 3-methylcrotonyl-CoA carboxylase deficiency (MCCD) was considered extremely rare before newborn screening (NBS) was undertaken but is now found in a number of asymptomatic babies or sometimes their mothers. This disorder of leucine metabolism, is the commonest organic aciduria found by screening, with a incidence of about 1:32 392 in our country. The clinical phenotype has been shown to vary considerably, ranging from entirely asymptomatic to death in infancy. A review of the literature on 37 individuals indicates that only 27% developed normally and stayed completely asymptomatic. Approximately 30% were reported to suffer from muscular hypotonia and psychomotor retardation, and almost half suffer from various other neurological symptoms. Even a lethality of 11% was observed. The metabolic phenotype characterizing MCCD is the elevated excretion of the diagnostic compounds 3-methylcrotonylglycine and 3-hydroxyisovaleric acid, and the presence of abnormally elevated blood levels of 3-hydroxyisovalerylcarnitine (C5-OH), as determined by tandem mass spectrometry (MS/MS). Patient and methods: The authors present a symptomatic case with an increase of C5-OH in the acylcarnitine profile who have a developmental delay. Blood spot samples from newborns are collected between day 3 and 6 in Watman 903 filter paper. Acylcarnitines in samples are analysed by MS/MS. Genes MCCA and MCCB that encodes the enzyme 3-MCC were studied by reported methods. Results: The molecular study has allowed the identification of the compound heterozygous in this patient: the frameshift mutation p.S173FfsX25 and the missense mutation p.V339M. Both mutations are described in the literature. Discussion: The newborn screening identification of a patient which developed symptoms seems to indicate that this disease should be included in NBS programs. More studies are needed to find genetic and/or biochemical markers that explain why a relatively small number of individuals are at risk of developing a severe disease phenotype. Another important reason to include MCCD in our panel is that other disorders are also detected by the marker C5OH; for example deficiencies of holocarboxylase synthetase, and 3-hydroxy- 3-methylglutaryl-CoA lyase.
URI: http://hdl.handle.net/10400.18/1172
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