CblC Type Methylmalonic Aciduria with a Novel Homozygous Mutation: A Case Report

Background CombinedMethylmalonic Aciduria (MMA), and homocystinuria CblC type is the most common inborn error of cobalamin metabolism with 77 mutations identified till date in the MMACHC gene. The disease has early and late presentations with varied clinical features. Case report A pair of preterm monochorionic twins was born to non-consanguineous parents with history of 2 previous infant deaths with suspected MMA. The twins became symptomatic in second week with severe neutropenia, thrombocytopenia, progressive encephalopathy and eczema without anemia, metabolic acidosis or hyperammonemia.  Investigation revealed elevated plasma Complement 3 (C3) acyl carnitine and very high MMA levels in urine. Genetic testing revealed a novel large deletion mutation in chromosome 1 which comprised of the whole MMACHC gene confirming the diagnosis of CblC type of MMA. The mutation was homozygous despite parents being unrelated and was identified in both parents later. Both twins responded transiently to treatment with hydroxycobalamin. Conclusion Large deletion in the MMACHC genewhich was identified in a homozygous state in our twins is previously unreported. The phenotypic features are described

Pediatric Index of Mortality and PIM2 Scores Have Good Calibration in a Large Cohort of Children from a Developing Country

Objective. Our objective was to validate the Pediatric Index of Mortality (PIM) and PIM2 scores in a large cohort of children from a developing country. Design. Prospective observational study. Setting. Pediatric intensive care unit of a tertiary care teaching hospital. Patients. All children aged <18 years admitted between June 2011 and July 2013. Measurements and Main Results. We evaluated the discriminative ability and calibration as measured by the area under the receiver operating characteristic (ROC) curves, the HosmerLemeshow goodness-of-fit (GOF), and standardized mortality ratio (SMR), respectively. Of the 819 children enrolled, 232 (28%) died. The median (IQR) age of the study subjects was 4 years (0.8, 10). The major reasons for ICU admission as well as mortality were sepsis/severe sepsis. The area under ROC curves for PIM and PIM2 was 0.72 (95% CI: 0.67-0.75) and 0.74 (95% CI: 0.70-0.78), respectively. The goodness-of-fit test showed a good calibration across deciles of risk for the two scores with values being >0.05. The SMR (95% CI) was 0.99 (0.85-1.15) and 1 (0.85-1.16) for PIM and PIM2, respectively. The calibration across different age and diagnostic subgroups was also good. Conclusion. PIM and PIM2 scores had good calibration in our setup

Pediatric Index of Mortality and PIM2 Scores Have Good Calibration in a Large Cohort of Children from a Developing Country

Objective. Our objective was to validate the Pediatric Index of Mortality (PIM) and PIM2 scores in a large cohort of children from a developing country. Design. Prospective observational study. Setting. Pediatric intensive care unit of a tertiary care teaching hospital. Patients. All children aged <18 years admitted between June 2011 and July 2013. Measurements and Main Results. We evaluated the discriminative ability and calibration as measured by the area under the receiver operating characteristic (ROC) curves, the Hosmer-Lemeshow goodness-of-fit (GOF), and standardized mortality ratio (SMR), respectively. Of the 819 children enrolled, 232 (28%) died. The median (IQR) age of the study subjects was 4 years (0.8, 10). The major reasons for ICU admission as well as mortality were sepsis/severe sepsis. The area under ROC curves for PIM and PIM2 was 0.72 (95% CI: 0.67–0.75) and 0.74 (95% CI: 0.70–0.78), respectively. The goodness-of-fit test showed a good calibration across deciles of risk for the two scores with P values being >0.05. The SMR (95% CI) was 0.99 (0.85–1.15) and 1 (0.85–1.16) for PIM and PIM2, respectively. The calibration across different age and diagnostic subgroups was also good. Conclusion. PIM and PIM2 scores had good calibration in our setup