Abstracts

Rationale: Mitochondrial DNA polymerase gamma (POLG) Alpers-Huttenlocher syndrome (AHS) can be associated with medication-resistant epilepsy. The ketogenic diet (KD) is an evidence-based treatment for medication-resistant epilepsy. The potential mechanism of action of the KD is glycolytic restriction resulting in increased fat utilization leading to a collective up-regulation of numerous energy metabolism genes and mitochondrial biogenesis. It is hypothesized that with POLG AHS there is an underlying problem with fat metabolism thus resulting in the affected tissues having increased energy requirements. Management of KD to treat epilepsy can be challenging for POLG AHS. Methods: We report on a 9 month old boy with status epilepticus admitted to the intensive care unit and treated with midazolam, high-dose phenobarbital, carbamazepine, clobazam, and topiramate. On day 8 of admission, a 3.5:1 ratio classic KD was initiated. To stabilize the patient's blood glucose (BG), maximize ketone production and stabilize weight, 19 diet modifications were made over a 64 day period. Our patient was diagnosed with POLG:C.1399G>A, POLG:C.2554C>T, POLG:C.32G>A mutations on day 39 of the KD. Results: A 648 kcal/d was initiated with an estimated 90% of daily caloric requirements, 2.5 g/d carbohydrate (CHO) at 3.5:1 ratio classic KD (CKD) prior to a known diagnosis. The patient had persistent hypoglycemia with BG levels between 2.4 to 2.7 mmol/L within the first 3 days of KD initiation. Despite this, urine ketones remained negative during this same time period. This unusual pattern supported the possible mitochondrial disorder that the neurology team was considering. To maximize the KD effect, 14 diet modifications were made by day 41 of KD to stabilize his BG>3.0 mmol/L and urine ketones at 8-16 mmol/L. By day 41, the diet provided 937 Kcal/d, 16.73 gm/d of CHO and the diet ratio was 4:1 CKD. Five more KD modifications were made to prevent his weight loss, adjust for a drop in ketosis and adjust formula at parental request to avoid artificial additives. L-Carnitine supplementation was added to correct his low carnitine levels from baseline and to KD. Parents reported fewer arm myoclonic jerks and increased alertness during the KD treatment. On day 64 of KD, patient's albumin level suddenly dropped from 38 to 18 g/L, AST up from 57 to 350 U/L and ALT up from 48 to 168 U/L. Both parents and health care team agreed to discontinue KD for patient safety. It was too soon to determine efficacy of the KD. At KD discontinuation, patient was on 980 Kcal/d 4.2:1 ratio for 3 meals and 4.5:1 ratio for bedtime snack CKD. Urine ketone levels had dropped to 0.5 mmol/L for 4 days and weight was stable at 9.6 Kg (101% IBW). Conclusions: Intensive monitoring and diet modification of the KD was necessary to stabilize the diet for this patient with POLG AHS. This may support the hypothesis of a possible underlying problem with fat metabolism found in this syndrome. Funding: N/A