A 12-year-old female suffering from adrenocortical insufficiency showed symptoms similar to a gastro-enteritis, and severe electrolytic and acid/base disturbances which progressed into cerebral oedema and death. Autopsy findings included depletion of the adrenal cortex, with enlargement and eosinophilia of surviving cells. In ante-mortem blood, anti-adrenal auto-antibodies were found and elevated levels of ACTH and cortisol with a low level of aldosterone.

INTRODUCTION There is limited understanding of relationships between genotype, phenotype and other conditions contributing to health in neonates with medium-chain acyl-coenzyme A dehydrogenase deficiency (MCADD) identified through newborn screening. METHODS Retrospective analysis of comprehensive data from a cohort of 221 newborn-screened subjects identified as affected with MCADD in the Inborn Errors of Metabolism – Information System (IBEM-IS), a long term follow-up database of the Inborn Errors of Metabolism Collaborative, was performed. RESULTS The average age at notification of first newborn screen results to primary care or metabolic providers was 7.45 days. The average octanoylcarnitine (C8) value on first newborn screen was 11.2 umol/L (median 8.6, range 0.36–43.91). A higher C8 level correlated with an earlier first subspecialty visit. Subjects with low birth weight had significantly lower C8 values. Significantly higher C8 values were found in symptomatic newborns, in newborns with abnormal lab testing in addition to newborn screening and/or diagnostic tests, and in subjects homozygous for the c.985A>G ACADM gene mutation or compound heterozygous for the c.985A>G mutation and deletions or other known highly deleterious mutations. Subjects with neonatal symptoms, or neonatal abnormal labs, or neonatal triggers were more likely to have at least one copy of the severe c.985A>G ACADM gene mutation. C8 and genotype category were significant predictors of the likelihood of having neonatal symptoms. Neonates with select triggers were more likely to have symptoms and laboratory abnormalities. CONCLUSIONS This collaborative study is the first in the United States to describe health associations of a large cohort of newborn-screened neonates identified as affected with MCADD. The IBEM-IS has utility as a platform to better understand the characteristics of individuals with newborn-screened conditions and their follow-up interactions with the health system.

REFERENCESBarth PG, Hoffman GE Jaeken J, et al (1994) We present two non-consanguineous Scottish families in whom definitive diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (MCADD; McKusick 201450), with homozygosity for the G985A mutation, was made in at least one surviving child, and where a presumably affected sibling had died in the neonatal period.Family A: A male infant (AI), born at 42 weeks' gestation weighing 3.05 kg, was initially well but collapsed at 48h. Bacteriological and viral infection screens were negative. Recurrent hypoglycaemia and seizures developed. Despite antibiotic treatment and resuscitative measures, including assisted ventilation, he died on day 6. Autopsy suggested myocarditis and cerebral oedema of unknown origin. Histological examination showed macrovesicular steatosis of the liver but no significant abnormality of renal tubules or myocardium. A2, brother of A1, was born at term and no neonatal complications were noted. He had "Reye syndrome' with marked ketonuria and hypoglycaemia at 17, 24 and 29 months and was eventually diagnosed as having MCADD. He is homozygous for the common North European A985G MCAD mutation. Fami(y B:A male full-term infant (B 1) was initially well, and was breast fed. On day 4 he collapsed, acidotic and bradycardic, and subsequently had a cardiac arrest. At postmortem, staphylococci were found in his spleen; his mother also had staphylococcal infection. Post-mortem slide review showed some hepatic macrovesicular fatty infiltration that in retrospect was consistent with MCADD. The myocardium was unremarkable, but renal tubular pallor was present. No fat staining was performed.

No abstract