PURA-Related Neurodevelopmental Disorders with Epilepsy Treated with Ketogenic Diet: A Case-Based Review

Area of Science:

• Genetics
• Neurodevelopmental disorders
• Metabolic therapies

Background:

• PURA syndrome is a rare congenital disorder resulting from de novo mutations in the PURA gene.
• The PURA gene encodes a crucial DNA/RNA-binding protein involved in gene regulation.
• Classical PURA deficiency presents with developmental delays and neurological issues.

Observation:

• An 11-year-old patient with a de novo frameshift variant in the PURA gene was identified via whole exome sequencing (WES).
• This patient exhibited classical PURA deficiency features alongside severe sialorrhea (drooling) and epilepsy (seizures).
• The patient's sialorrhea and seizures showed significant improvement following the implementation of a ketogenic diet (KD).

Findings:

• This case documents the first instance of successful management of sialorrhea and seizures in PURA syndrome using a ketogenic diet.
• A novel frameshift deletion in the PURA gene was identified, expanding the known spectrum of genetic variants associated with the syndrome.
• While a direct mechanistic link was not established, the clinical response to KD suggests a potential metabolic or neurological pathway influenced by the PURA mutation.

Implications:

• The findings suggest that ketogenic diet therapy may be a viable therapeutic option for managing specific symptoms in PURA syndrome.
• This case highlights the importance of considering metabolic interventions for neurological manifestations in rare genetic disorders.
• Further research is warranted to elucidate the potential mechanisms underlying the efficacy of KD in this context and its broader applicability.