Newborn screening for medium-chain acyl-CoA dehydrogenase deficiency: regional experience and high incidence of carnitine deficiency

Orphanet Journal of Rare Diseases

Hugo Rocha³  José M Fraga⁵  Antonia Ribes⁶  Judit García-Villoria⁶  José A Cocho⁹  Daisy E Castiñeiras⁹  Carmen Delgado-Pecellín⁴  Maria Amor Bueno¹  Helena Santos²  Esmeralda Martins^1,10  Elisa Leão-Teles⁸  Luisa Diogo⁷  Paula Sánchez-Pintos⁵  Maria Luz Couce⁵ 

[1] Unidad de Metabolopatías y Nutrición Infantil, Departamento de Pediatría, Hospital Universitario Virgen del Rocio, Sevilla, Spain;Departamento de Pediatria, Centro Hospitalar Gaia/Espinho, Gaia, Portugal;Unidade de Rastreio Neonatal, Departamento de Genética do Instituto Nacional de Saúde Doutor Ricardo Jorge, Porto, Portugal;Departamento de Bioquímica Clínica, Hospital Universitario Virgen del Rocío, Sevilla, Spain;Unidad de Diagnóstico y Tratamiento de Enfermedades Congénitas del Metabolismo, Departamento de Pediatría, Hospital Clínico Universitario, Universidad de Santiago, Santiago de Compostela, Spain;Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica y Genética Molecular, Hospital Clínic y Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Barcelona, Spain;Centro de Desenvolvimento da Criança Luís Borges, Hospital Pediátrico de Coimbra, Coimbra, Portugal;Unidade Doenças Metabólicas, Hospital Pediátrico Integrado, Centro Hospitalar de S. João, EPE, Porto, Portugal;Unidad de Diagnóstico y Tratamiento de Enfermedades Congénitas del Metabolismo, Laboratorio de Metabolopatías, Hospital Clínico Universitario, Universidad de Santiago, Santiago de Compostela, Spain;Unidade de Doenças Metabólicas, Hospital de Crianças Maria Pia, Centro Hospitalar do Porto, Porto, Portugal

关键词: Rare disease;    Newborn screening;    Mutations;    Mitochondrial fatty acid oxidation;    Metabolic decompensation;    L-carnitine;   

Others  :  863662
DOI  :  10.1186/1750-1172-8-102

 received in 2013-03-07, accepted in 2013-07-05,  发布年份 2013

【 摘 要 】

Background

Medium-chain acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited defect in the mitochondrial fatty acid oxidation pathway, resulting in significant morbidity and mortality in undiagnosed patients.

Newborn screening (NBS) has considerably improved MCADD outcome, but the risk of complication remains in some patients. The aim of this study was to evaluate the relationship between genotype, biochemical parameters and clinical data at diagnosis and during follow-up, in order to optimize monitoring of these patients.

Methods

We carried out a multicenter study in southwest Europe, of MCADD patients detected by NBS. Evaluated NBS data included free carnitine (C0) and the acylcarnitines C8, C10, C10:1 together with C8/C2 and C8/C10 ratios, clinical presentation parameters and genotype, in 45 patients. Follow-up data included C0 levels, duration of carnitine supplementation and occurrence of metabolic crises.

Results

C8/C2 ratio and C8 were the most accurate biomarkers of MCADD in NBS. We found a high number of patients homozygous for the prevalent c.985A > G mutation (75%). Moreover, in these patients C8, C8/C10 and C8/C2 were higher than in patients with other genotypes, while median value of C0 was significantly lower (23 μmol/L vs 36 μmol/L).

The average follow-up period was 43 months. To keep carnitine levels within the normal range, carnitine supplementation was required in 82% of patients, and for a longer period in patients homozygotes for the c.985A>G mutation than in patients with other genotypes (average 31 vs 18 months). Even with treatment, median C0 levels remained lower in homozygous patients than in those with other genotypes (14 μmol/L vs 22 μmol/L).

Two patients died and another three suffered a metabolic crisis, all of whom were homozygous for the c.985 A>G mutation.

Conclusions

Our data show a direct association between homozygosity for c.985A>G and lower carnitine values at diagnosis, and a higher dose of carnitine supplementation for maintenance within the normal range. This study contributes to a better understanding of the relationship between genotype and phenotype in newborn patients with MCADD detected through screening which could be useful in improving follow-up strategies and clinical outcome.

【 授权许可】

   
2013 Couce et al.; licensee BioMed Central Ltd.

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