Ketogenic diet in two brothers with pyruvate dehydrogenase deficiency

Ketogenic diet is the treatment of choice in patients with pyruvate dehydrogenase deficiency. An early initiation of the diet is associated with a better outcome.

Patient 1: Soon after birth a mild hypotonia was diagnosed. At age 1 year the boy showed a global developmental delay and an extensive work-up was initiated. Due to an intermittent slightly elevated lactate a muscle biopsy was taken. A reduced activity of the PDH-complex was found. After the diagnosis at age 2 years he was started on ketogenic diet. Soon afterwards his psychomotor function improved and he learned to walk. At age 5 years he developed focal seizures. The ketogenic diet at this point was not efficient, due to non-adherence to the dietary restrictions. At age nine he is able to walk, needs help in every daily activities and has no speech. Whenever his blood keton gets low, he suffers more seizures. Side effects of the diet is a hypercholesterolemia.

Patient 2: He is a maternal half-brother of patient-1. He was born per elective C-section at 37+2 weeks gestational age. Pregnancy was uncomplicated. Due to feeding problems the infant was transferred to a pediatric unit at day 2. He was feed by nasogastral tube. Additionally he showed recurrent apnoe and an elevated CO2. An EEG showed burst suppression on day 7. He was transferred for further tests and treatment to our unit on day 15. He had a normal pre-prandial lactate and a slightly elevated postprandial lactate (3mmol/l). Because of the positive family history of PDH and a supposed X-linked inheritance we initiated ketogenic diet (ratio 3:1). Initiation of the diet was uncomplicated. The patient thrived well. At age 1 month the patient developed tonic-clonic seizures, which responded well to Phenobarbital treatment. Within a week after initiating the ketogenic diet, the patient seemed to improve. He was more alert, the apnoe were no longer noted. The hypotonia improved, however, movements were not normal but suggestive of a developing cerebral palsy. Due to abdominal problems we reduced the ratio after 4 month to a ratio of 2,5:1. At age 5 month he was able to feed on his own. No side effects have so far been noted.

Discussion: We present two boys with pyruvate dehydrogenase deficiency. Both boys improved with ketogenic diet. The younger boy tolerated the initiation of the diet at a very young age of 15 days very well, the diet showed no side effects and the boy thrived well.

The younger boy is clinically more severely affected than the older. The older brother had no feeding problems after birth, a normal breathing pattern and only a mild hypotonia. He developed seizures at age 5 years. Therefore we cannot compare the effect of early initiation of the ketogenic diet on the developmental outcome of both boys.