# Neonatal Presentation of Ornithine Transcarbamylase Deficiency Associated With a Hypomorphic OTC Variant (p.Leu301Phe) Previously Reported in Later-Onset Disease

## TL;DR

A newborn with a specific OTC gene variant showed early signs of a rare metabolic disorder, requiring immediate medical intervention.

## Contribution

This case demonstrates that a previously reported OTC variant can cause neonatal symptoms, necessitating early management.

## Key findings

- A male newborn with the p.Leu301Phe OTC variant presented with neonatal hyperammonemia despite being asymptomatic.
- Management with low-protein formula and ammonia scavengers normalized ammonia levels in the patient.
- The case confirms the variant's pathogenicity and highlights the need for early intervention in affected newborns.

## Abstract

Ornithine transcarbamylase deficiency (OTCD) is the most common subtype of urea cycle disorders. Caused by mutations in the X-linked gene OTC,it often leads to hyperammonemia which can result in neurotoxicity, coma, and death. We describe the clinical course of a male newborn known to carry a hypomorphic variant (p.Leu301Phe) in OTC previously reported in cases with later-onset OTCD. Despite being clinically asymptomatic, our affected patient presented with hyperammonemia in the neonatal period. Oral feedings were temporarily discontinued, and low protein medical formula and ammonia scavenger medications were initiated to normalize ammonia levels. This case supports the pathogenicity of the reported OTC gene variant and early presentation that necessitates disease-specific management. Our report will help provide guidance surrounding the most appropriate management of future patients with this variant as they will likely require management in the newborn period.