Successful implementation of ketogenic diet in a TRIT1 deficient patient with diabetes mellitus leads to clinical improvement

Background

We present a girl followed up for microcephaly, progressive spastic tetraplegia, epilepsy, feeding difficulties and cognitive impairment. At the age of 8 years she developed pancreatitis, liver dysfunction and increased lactate (1,5-2,8 mmol/l). Mitochondrial dysfunction was suspected. Genetic analysis revealed compound heterozygous pathogenic variants in TRIT1, resulting in a combined oxidative phosphorylation deficiency. She developed diabetes mellitus (DM) for which insulin therapy was started. Facing the beneficial effects of ketogenic diet in one previously reported TRIT1 deficient patient, we considered its implementation for this girl.

Case Study

The girl was tube fed with a hydrolysed tube feed, 4 x 260 ml per day. She received 58 kcal/kg/day and 1,6 g protein per kg/day. She received 7 units of subcutaneous rapid acting insulin 15 minutes before day feed and 8,5 units of long acting insulin before night feed. Each feeding time lasted 55 minutes. Her average glycemia was 14 mmol/l the month before diet change. Ketogenic diet, with a ratio of 3:1, was implemented over 4 days. Insulin therapy was adapted until stable glycemia.

Results

Full ketosis was achieved at the end of day 4 with 4 x 260 mL of ketogenic tube feeding ratio 3:1 (60 kcal/kg/day and 1,7 g of protein per kg/day). Average glycemia was 9,4 mmol/l during diet change. Ketosis was easily reached, but insulin scheme had to be adapted sequential because of daytime and night hypoglycaemia. Consequently ketosis of >6 mmol/l was observed, forcing a tapering of the ratio to 2.5:1. Four months after onset, we observe a stable condition and clinical improvement with no recurrency of pancreatitis and lower lactate levels (<1.5 mmol/l).

Discussion

Implementation of ketogenic diet in a TRIT1 deficient patient with DM is feasible and leads to clinical improvement.