Neonatal pulmonary haemorrhage: presentation of a medium-chain acyl-CoA dehydrogenase deficiency

CASE DESCRIPTION : After an uncomplicated term pregnancy and delivery, a two-days-old infant presented with poor feeding, grunting and prolonged capillary refill. Apart from hypothermia, the patient's vital signs were normal. The blood glucose level was 24 mg/dL needing correction. Broadspectrum antibiotics were initiated. The patient's respiratory and neurological condition rapidly deteriorated requiring mechanical ventilation. Intubation was followed by fresh blood filling the tube. Endotracheal suctioning cleared large quantities of blood. Arterial blood gas analysis revealed a primary metabolic acidosis with full respiratory compensation and in serum an increased anion gap was found. Chest X-ray showed patchy bilateral pulmonary infiltrates. CT confirmed massive pulmonary infiltrates but could not identify an underlying intra-thoracal lesion. Echocardiography and bronchoscopy were strictly normal. Metabolic review showed normal blood levels of ureum and lactate, a mild hyperammonemia and a low bicarbonate. Creatinine, AST and ALT levels were normal. Coagulation was disrupted with a prolonged aPTT, normal PT, low fibrinogen and normal platelet count. This was corrected by administration of fresh frozen plasma. The patient received several packed red cell transfusions to correct anaemia. Mechanical ventilation was continued for 6 days, weaning was uncomplicated. Results from routine newborn screening showed increased levels of C8 and C10:1 in the acylcarnitine profile. Urinary organic acid profile fitted the diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency and DNA analysis confirmed the diagnosis by demonstrating a homozygous c.985A>G mutation in the encoding ACADM gene. Parents were given advice on how to avoid fasting and L-carnitine supplementation was initiated. At 8 months of age, the infant demonstrates normal growth and development. CONCLUSION : MCAD deficiency is the most common inherited disorder of fatty-acid beta-oxidation. Its first sign is most frequently an episode of encephalopathy. In this case, encephalopathy probably started on the second day of life and caused (further) inadequate feeding. The rapidly progressive respiratory symptoms however, dominated the clinical presentation. Pulmonary haemorrhage (PH) has previously been reported in four post-mortem cases of MCAD deficiency and in one surviving case. As cardiac function was normal in the current case, the previously suggested hypothesis of primary cardiac dysfunction as a cause of PH in MCAD deficiency is now less probable. A bleeding diathesis was the only identified risk factor for PH in our case. Mouse models suggest a direct link between beta-oxidation defects and coagulation disorders but the precise mechanism remains to be elucidated. This case report also illustrates the importance of aggressive supportive therapy in acutely ill infants in which a metabolic disorder is suspected. Early diagnosis can allow early transition from supportive to specific therapy to prevent future crises and optimise neurological development