Medium-chain Acyl-CoA dehydrogenase deficiency presenting with neonatal pulmonary haemorrhage

Abstract

Background: Medium-chain Acyl-CoA dehydrogenase deficiency (MCADD) is the most common inherited disorder of fatty acid beta-oxidation. Signs and symptoms of MCADD typically appear during infancy or early childhood and include vomiting, lethargy, and hypoglycemia. Pulmonary haemorrhage has previously been described in patients with MCADD, but has always been considered a pre-terminal complication caused by heart failure.

Case presentation: We report on a newborn term infant that presented on the second day of life with signs of encephalopathy, followed by hypovolemia and respiratory distress caused by a severe pulmonary haemorrhage. Fluid resuscitation and mechanical ventilation were initiated and the coagulopathy was corrected by the administration of fresh frozen plasma. Echocardiography revealed a normal cardiac function. After 6 days of full intensive care, the patient survived without sequellae. The clinical presentation in absence of signs of infection raised a strong suspicion for a metabolic disorder and genetic testing revealed MCADD due to a homozygous A985G mutation.

Conclusion: The key towards successful management of severe pulmonary haemorrhage in newborns with a coagulopathy and suspicion of an underlying metabolic disorder consists of adequate mechanical ventilation and aggressive use of fresh frozen plasma, while treating the metabolic decompensation and initiating an early diagnostic work-up. MCADD can lead to acute decompensation and present with complications such as pulmonary haemorrhage independent of cardiac function. Hence, in the context of MCADD, pulmonary haemorrhage should not be considered a pre-terminal complication caused by heart failure, and rather than withdrawing care, intensive treatment must be initiated.

Keywords: Medium-chain Acyl-CoA Dehydrogenase Deficiency (#MIM 201450); Pulmonary haemorrhage.

Figure 1

Chest X-rays showing bilateral patchy infiltrates due to pulmonary hemorrhage on admission and resolution upon discharge.

Figure 2

Timeline showing work-up to diagnosis of MCADD. ACADM: acyl-CoA dehydrogenase, C-4 to C-12 straight chain (MIM:607008), ALT: Alanine transaminase, AST: Aspartate transaminase, CK: Creatine kinase, CRP: C-reactive protein, PH: pulmonary haemorrhage.