Fatty acid oxidation disorders: outcome and long‐term prognosis

Assessing the outcome of fatty acid oxidation disorders is difficult, as most are rare. For diagnosis by newborn screening, the situation is compounded: far more cases are diagnosed by screening than by clinical presentation, representing a somewhat different cohort. The literature on outcome was reviewed. For disorders other than medium‐chain acyl‐coenzyme A (CoA) dehydrogenase (MCAD) deficiency there was insufficient evidence to make many firm statements. In MCAD deficiency, risk of death in the first 72 h is around 4%, with a further approximately 5–7% fatality rate in the first 6 years but very low subsequent risk in previously undiagnosed patients. The risk of death after diagnosis is very low at any age, with good management. The long‐term outcome is good nowadays. Very‐long‐chain acyl‐CoA dehydrogenase deficiency poses a risk of death in early infancy, but the condition is generally treatable, with a good outcome after diagnosis. Approximately 10–20% of patients diagnosed by newborn screening and treated nevertheless suffer episodic rhabdomyolysis. Some patients never become symptomatic. Isolated long‐chain 3‐hydroxyacyl‐CoA dehydrogenase deficiency is treatable, but most patients suffer episodic hypoketotic hypoglycaemia and rhabdomyolysis. Generalised mitochondrial tri‐functional protein deficiency has high early mortality rate. A more insidious presentation also occurs, with symptoms sometimes confined to progressive axonal neuropathy. Among carnitine cycle disorders, carnitine transporter deficiency, potentially lethal, is uniformly successfully treated orally with carnitine. Carnitine‐acylcarnitine translocase and early‐onset carnitine palmitoyl transferase type II (CPT II) deficiencies have an extremely high neonatal mortality rate. Late‐onset CPT II is characterised only by episodic rhabdomyolysis on severe exercise. CPT type IA deficiency may often be benign, although early presentation with hypoketotic hypoglycaemia certainly occurs.