PRKAG2 mutations presenting in infancy.

Area of Science:

• Genetics
• Cardiology
• Metabolic Disorders

Background:

• PRKAG2 gene encodes the AMP-activated protein kinase (AMPK) gamma-2 subunit, crucial for cardiac metabolism.
• Mutations in PRKAG2 are linked to a cardiac syndrome (ventricular hypertrophy, pre-excitation, conduction disease), typically diagnosed in adolescence/adulthood.
• Infantile presentation of PRKAG2-related cardiac syndrome is underrecognized and challenging to diagnose.

Observation:

• Three infant cases initially suspected of having Pompe disease were ultimately diagnosed with PRKAG2 mutations.
• A novel PRKAG2 missense mutation was identified in one patient.
• PRKAG2 mutations can present symptomatically in infancy, mimicking other genetic metabolic disorders.

Findings:

• Confirms that PRKAG2 mutations can manifest in infancy with symptoms overlapping those of Pompe disease.
• Identifies a novel disease-causing mutation in the PRKAG2 gene.
• Demonstrates the diagnostic challenge in differentiating PRKAG2 cardiac syndrome from Pompe disease in infants.

Implications:

• Highlights the critical need for genetic testing for PRKAG2 mutations in infants presenting with cardiac symptoms suggestive of Pompe disease.
• Suggests that earlier diagnosis of PRKAG2-related cardiac syndrome is possible with increased clinical awareness.
• Emphasizes the importance of comprehensive genetic evaluation to avoid misdiagnosis and ensure appropriate management of infantile cardiac conditions.