G473 Primary carnitine deficiency: variable in its presentation, treatable in its course and the importance of family screening. A case series

Background Primary carnitine deficiency (PCD) is an autosomal recessive disorder of fatty acid oxidation, caused by mutations in the SLC22A5 gene encoding for the carnitine transporter OCTN2. Carnitine uptake deficiency prevents the body from using certain fats for energy, particularly during periods of fasting or illness. The first manifestation of PCD can be at any age, where patients can present with hypoglycemia, hyperammonaemia, encephalopathy, skeletal myopathy and cardiomyopathy. Case Review We report on a previously well 15 year old boy who participated in a challenging Duke of Edinburgh expedition. The following morning he was found drowsy and subsequently admitted to hospital with worsening encephalopathy, hypoglycaemia and hyperammonaemia. This, along with rising CK and troponin levels meant PCD was included in the early differential and carnitine supplementation was commenced. Unfortunately his cardiac failure was too advanced and he had a cardiac arrest, dying after an hour of CPR. Genetic testing confirmed the diagnosis of PCD. On family cascade screening his asymptomatic sister was also diagnosed with PCD, started on oral carnitine supplements and continues to be well. A retrospective analysis of a total of thirteen diagnosed patients from one centre illustrates the variability of first presentation of PCD. Five children (ranging between 2 months and 7 years) presented with cardiac symptoms; four with cardiomyopathy, one with a cardiac arrest. Two children presented between 1 year and 3 years with hypoketotic hypoglycaemia. Two children presented with muscle fatigability at 7 months and 7 years of age. Another presented at 10 months old with motor regression, failure to thrive and an abnormal ECG. Two children were diagnosed at birth, either by newborn or sibling screening. Conclusion This case series illustrates that PCD can present at any age with variable symptoms. Although rare, PCD should always be considered in patients with unexplained symptoms including encephalopathy. It is potentially lethal, but also extremely treatable, as early carnitine supplementation equates to excellent prognosis. Lastly, our case highlights the importance of family screening in preventing potential fatalities.