Methylmalonic acidemia presenting as persistent pulmonary hypertension of the newborn

Persistent pulmonary hypertension of the newborn (PPHN) results from disruption of the normal fetal-neonatal circulatory transition and may be associated with meconium aspiration, group B streptococcal sepsis, pneumonia, respiratory distress syndrome, congenital diaphragmatic hernia and pulmonary hypoplasia. Seventeen percent of cases are considered idiopathic since there is no identifiable cause. Although it is recognized that acidosis and hypoxia from any cause in neonates may produce pulmonary vasoconstriction and maintain pulmonary hypertension, PPHN has not been reported in inborn errors of metabolism (IEM) associated with metabolic acidosis like methyl malonic acidemia (MMA). We report the first case in the literature of MMA presenting concomitantly with PPHN. Undiagnosed IEMs, like MMA, could represent a subset of idiopathic cases of PPHN. Infants and neonates have a limited repertoire with which to respond to an overwhelming illness. Because metabolic diseases are rare, they are considered only after excluding more common causes of neonatal distress. PPHN is therefore more likely to be attributed to meconium aspiration, sepsis, pneumonia or respiratory distress syndrome than to an IEM. The advent of expanded newborn screening has made pre-symptomatic diagnosis of several IEMs including MMA possible. However, not all IEMs are identified, and in some instances, an infant who has an IEM may become ill before the results of the newborn screen become available. Early diagnosis of IEM is crucial to prevent catastrophic consequences and the awareness of an association with PPHN would lead to an aggressive search of an underlying IEM and its management.