# A DNA Polymerase Subunit Gamma (POLG) Mutation Imposing a Difficult Differential Diagnosis of Hepatic Encephalopathy in a Newborn: A Case Report

## TL;DR

A rare POLG mutation in a newborn caused severe liver failure and encephalopathy, complicating diagnosis and leading to a poor outcome.

## Contribution

This is the first reported case of a specific POLG mutation (NM_002693.3(POLG):c.3104+2T>A) causing hepatic encephalopathy in an infant.

## Key findings

- The patient exhibited acute hepatic failure and encephalopathy with no response to treatment.
- A postmortem genetic test confirmed a rare POLG mutation (Variation ID: 422378).
- The case highlights the importance of early screening for mitochondrial mutations in similar clinical presentations.

## Abstract

Hepatic encephalopathy (HE) is a condition connected with neuropsychiatric alteration during hepatic failure. The differential diagnosis of HE is challenging due to overlapping symptoms with other conditions. Polymerase subunit gamma (POLG) is a mitochondrial gene, and an infant POLG mutation can manifest with severe and progressive hepatic failure and encephalopathy, imposing a difficult differential diagnosis due to similarities to other conditions. The lack of curative treatment leads to a poor prognosis.

An 11-month-old boy was admitted to the intensive care unit (ICU) due to altered consciousness and increasing edema due to acute hepatic failure of unknown etiology. After extensive multidisciplinary discussions and a lack of response to treatment for more than three weeks, a mitochondrial disease was suspected, and a genetic test was taken. The patient’s condition continued to deteriorate. The patient died on the 25th day of hospitalization in the ICU. After death, a genetic test confirmed a rare POLG mutation NM_002693.3(POLG):c.3104+2T>A (Variation ID: 422378 Accession: VCV000422378.8).

We suggest that a screen test for POLG mutations be considered early in the diagnostic process and that clinicians consider mitochondrial genetic mutations, such as POLG mutations, more often. This article is the first to describe a patient with this specific mutation.