RESUMEN
The aim of this study was to identify the causative genetic lesion in two apparently unrelated newborns having lethal lactic acidosis, multi-organ failure and congenital malformations including interrupted aortic arch, who exhibited mild methylmalonic aciduria, combined mitochondrial respiratory chain deficiency, and marked muscle mitochondrial DNA depletion. A novel mutation in the SUCLG1 gene was identified. Phenotype severity in Succinate-CoA ligase dysfunction appears to be more correlated to the muscle mtDNA content than to the tissue distribution of the heterodimer subunits. Prominent impairment of mitochondrial respiratory chain may result in deep ravages in developmental tissues leading to multiple organ failure and malformations.
Asunto(s)
Acidosis/genética , Aorta Torácica/anomalías , Enfermedades Genéticas Congénitas/diagnóstico , Proteínas Mitocondriales/deficiencia , Insuficiencia Multiorgánica/congénito , Mutación Missense , Succinato-CoA Ligasas/deficiencia , ADN Mitocondrial/genética , Resultado Fatal , Femenino , Enfermedades Genéticas Congénitas/patología , Humanos , Recién Nacido , Masculino , Ácido Metilmalónico/orina , Insuficiencia Multiorgánica/genética , Músculos/patologíaAsunto(s)
Enfermedades Fetales/diagnóstico , Diagnóstico Prenatal , Tumor Rabdoide/diagnóstico , Rotura Espontánea/patología , Adulto , Brazo , Resultado Fatal , Femenino , Humanos , Insuficiencia Multiorgánica/congénito , Insuficiencia Multiorgánica/patología , Embarazo , Tercer Trimestre del Embarazo , Tumor Rabdoide/congénito , Rotura Espontánea/congénitoRESUMEN
Transaldolase (TALDO) deficiency is a newly recognized metabolic disease, which has been reported so far in 2 patients presenting with liver failure and cirrhosis. We report a new sibship of 4 infants born to the same consanguineous parents; all presented at birth or in the antenatal period with dysmorphic features, cutis laxa and hypertrichosis, hepatomegaly, splenomegaly, liver failure, hemolytic anemia, thrombocytopenia, and genitourinary malformations. The clinical courses were variable: the first child died of liver failure at 4 months of age; the second pregnancy was medically terminated at 28 weeks gestation because of hydrops fetalis with oligohydramnios. The third child is doing well at age 7 with liver fibrosis and mild kidney failure. The fourth child is now 21 months old and has hepatosplenomegaly, mild anemia, and thrombocytopenia. Urine assessment of polyols showed elevations of erythritol, arabitol, and ribitol consistent with TALDO deficiency. TALDO activity was undetectable in the patients' tissues, and mutation in the TALDO1 gene was found in the 4 patients.
Asunto(s)
Hidropesía Fetal/enzimología , Insuficiencia Multiorgánica/enzimología , Transaldolasa/deficiencia , Biomarcadores/orina , Consanguinidad , Eritritol/orina , Resultado Fatal , Femenino , Enfermedades Fetales/enzimología , Enfermedades Fetales/patología , Eliminación de Gen , Humanos , Hidropesía Fetal/orina , Recién Nacido , Masculino , Insuficiencia Multiorgánica/congénito , Insuficiencia Multiorgánica/orina , Ribitol/orina , Alcoholes del Azúcar/orina , Transaldolasa/genética , TurquíaRESUMEN
OBJECTIVE: The purpose of this study was to determine the significance of fetal acidemia for newborn encephalopathy (NEP) and for the combination of NEP and multiorgan system dysfunction (MOS). In particular the influence of acidemia will be contrasted with criteria of pregnancy and delivery. STUDY DESIGN: 248 infants delivered with cord umbilical arterial pH < 7.15 (UApH) were retrospectively studied. Infants with similar or identical neonatal characteristics formed different groups: unaffected neonatal development, NEP, NEMO (NEP combined with MOS), other diseases, infection, exitus letalis. Statistics and calculations were done by means of factor analysis, univariate analysis, Student-Newman-Keuls-test, and Chi 2-test (p < 0.05). RESULTS: Twenty seven infants with UApH < 7.15 suffered from NEP. NEP in combination with MOS occurred in 11 cases. There was no relationship between the degree of acidemia and a single NEP. Infants with NEMO differ from all other groups in their mean UApH (p < 0.05). The Apgar scores 1 min and 5 min (A1, A5) separated newborns with unaffected neonatal development from all other groups (p < 0.05). UApH-differences in the group: NEMO resulted from a combination of acute intranatal fetal distress and operative delivery and a combination of A1, A5, preterm delivery, and pathologic CTG (p < 0.01). CONCLUSIONS: The degree of acidemia impacts the occurrence of NEMO. However, UApH alone does not predict this combination of characteristics. The Apgar score should be taken into account to evaluate an acidemic UApH. In case of acidemia complex factors of pregnancy and delivery are associated with an increased risk of NEMO.