RESUMO
We report a positive newborn screen for 3-hydroxyisovalerylcarnitine (C(5)OH) with an absence of 3-methylcrotonyl-coenzyme A carboxylase deficiency in the neonate. Subsequent blood tests demonstrated persistently elevated C(5)OH. Serial testing of the mother identified markedly elevated C(5)OH in both maternal blood and breast milk. High C(5)OH milk concentrations provide a significant source of C(5)OH to the nursing neonate and possibly explains its persistent elevation in the neonate, a commonly observed finding in maternal 3-MCC deficiency.
Assuntos
Carbono-Carbono Ligases/deficiência , Carnitina/análogos & derivados , Leite Humano/química , Carnitina/metabolismo , Feminino , Humanos , Recém-Nascido , Triagem NeonatalRESUMO
Mutations in the SLC25A15 gene, encoding the human inner mitochondrial membrane ornithine transporter, are thought to be responsible for hyperornithinemia-hyperammonemia-homocitrullinemia (HHH) syndrome, a rare autosomal recessive condition. HHH syndrome has been detected in several small, isolated communities in northern Saskatchewan (SK). To determine the incidence of HHH syndrome in these communities, a PCR method was set up to detect F188Δ, the common French-Canadian mutation. Neonatal blood spots collected from all newborns from the high risk area were genotyped for the F188Δ mutation for seven consecutive years. Using DNA analysis, we estimated that the heterozygote frequency for the mutant allele for HHH syndrome to be about 1 in 19 individuals, predicting one affected child with HHH syndrome for approximately every 1,500 individuals (1 in 1,550 live births; 1 child every 12 years) in this isolated population. The frequency for the mutant allele for HHH syndrome in this isolated community is probably the highest in the world for this rare disorder. We determined that ornithine levels, by tandem mass spectrometry, were not abnormal in newborns with F188Δ mutation, carriers and normals. Ornithine rises to abnormally high levels at some time after birth well past the time that the newborn screening blood spot is collected. The timing or the reasons for the delayed rise of ornithine in affected children with HHH syndrome have not been determined. Newborn screening for HHH Syndrome in this high risk population is only possible by detection of the mutant allele using DNA analysis.
Assuntos
Sistemas de Transporte de Aminoácidos Básicos/genética , Análise Mutacional de DNA , Testes Genéticos/métodos , Hiperamonemia/diagnóstico , Hiperamonemia/epidemiologia , Mutação , Triagem Neonatal/métodos , Ornitina/deficiência , Distúrbios Congênitos do Ciclo da Ureia/diagnóstico , Distúrbios Congênitos do Ciclo da Ureia/epidemiologia , Biomarcadores/sangue , Teste em Amostras de Sangue Seco , Frequência do Gene , Predisposição Genética para Doença , Heterozigoto , Homozigoto , Humanos , Hiperamonemia/sangue , Hiperamonemia/genética , Incidência , Recém-Nascido , Proteínas de Transporte da Membrana Mitocondrial , Ornitina/sangue , Ornitina/genética , Fenótipo , Reação em Cadeia da Polimerase , Valor Preditivo dos Testes , Estudos Prospectivos , Estudos Retrospectivos , Saskatchewan/epidemiologia , Espectrometria de Massas em Tandem , Fatores de Tempo , Distúrbios Congênitos do Ciclo da Ureia/sangue , Distúrbios Congênitos do Ciclo da Ureia/genéticaRESUMO
OBJECTIVES: To assess the Architect i2000 for measuring TSH from neonatal blood spots. METHODS: Blood collected on filter paper was eluted and assayed on the Architect. RESULTS: Recovery of TSH was close to 100%. Within-run and between-run precisions were 4.2-8.2% and 14.5-18.1%. Correlation with the Wallac Delphia method was excellent (r = 0.96). Linearity, sensitivity, and slope were 0-400 mU/l, 0.15 mU/l, and 0.86, respectively. The results obtained by this method on the Architect allowed us to differentiate normals from affected patients with the same reliability as the previous method. CONCLUSIONS: Measurement of TSH on the Architect is an excellent method for detecting congenital hypothyroidism.