Combined Oxidative Phosphorylation Deficiency Type-13 with Perinatal Presentation: A Case Report

Area of Science:

• Genetics
• Mitochondrial Biology
• Neurology

Background:

• Polynucleotide phosphorylase (PNPT1) is crucial for mitochondrial RNA processing.
• Biallelic variants in PNPT1 lead to mitochondrial RNA import protein deficiency.
• This deficiency results in diverse and severe clinical manifestations.

Purpose of the Study:

• To describe a novel case of PNPT1 gene mutation presenting with early-onset, severe Leigh syndrome.
• To expand the known phenotypic spectrum of PNPT1-associated disorders.
• To emphasize the utility of whole exome sequencing (WES) in diagnosing rare genetic conditions.

Main Methods:

• Detailed clinical case report of an infant with severe perinatal symptoms.
• Neuroimaging (MRI) to assess brain structure and pathology.
• Whole exome sequencing (WES) for genetic variant identification.

Main Results:

• The patient presented with severe neonatal distress, global developmental delay, Leigh syndrome-like brain lesions, and hypertrophic cardiomyopathy.
• Whole exome sequencing identified a homozygous likely pathogenic variant in the PNPT1 gene.
• This represents the first reported case of PNPT1 mutation with perinatal onset and associated hypertrophic cardiomyopathy.

Conclusions:

• The early and severe Leigh-like presentation, including hypertrophic cardiomyopathy, expands the known phenotype of PNPT1 mutations.
• This case is the first reported PNPT1 mutation presenting in the perinatal period.
• Whole exome sequencing is critical for the early diagnosis of severe, unexplained pediatric conditions.