Background:
Although research regarding POLG1 mutations is plentiful, little is known regarding a related gene, POLG2. This gene encodes for an accessory subunit in the DNA polymerase gamma, which helps translate nuclear DNA into mitochondrial DNA. POLG mutations can often cause mitochondrial deletion syndrome, which can lead to liver failure and intractable seizures. Most cases of POLG2 are reported as variations of progressive external ophthalmoplegia or ataxia. Here we present a case of an infant with a bi-allelic POLG2 mutation leading to hepatic failure and epilepsy.
Results:
A 5-week-old, former full term healthy female born to two healthy parents presented in status epilepticus requiring intubation and midazolam drip. Workup revealed normal LP and MRI brain without contrast. MRI spectroscopy of brain showed a small lactate peak but still within limits for age. Seizures responded to levetiracetam, and the patient was weaned off midazolam and discharged home without complication while metabolic investigation was pending. Three days later, the patient re-presented for bilious emesis and poor feeding. Labs showed significant transaminitis, coagulopathy, anemia, and hypoglycemia. Repeat EEG initially did not show seizures. On hospital day 8, patient started having subtle arm and head jerking, concerning for focal seizures. Over the following 48 hours, she developed epilepsia partialis continua (EPC) which responded well to lacosamide administration. Rapid trio whole exome sequencing revealed bi-allelic variants in POLG2. The first variant was paternally inherited and was classified as likely pathogenic due to a premature stop codon. The second variant was classified as a variant of unknown significance and was maternally inherited. Concomitantly, her ammonia continued to uptrend and coagulopathy worsened, suggestive of fulminant liver failure. Patient passed away at 8 weeks old.
Conclusions:
Although POLG1 is widely known, here we present a case of bi-allelic POLG2 mutation that led to epilepsy, liver failure, and eventually death.