Identification of SLC22A5 Gene Mutation in a Family with Carnitine Uptake Defect

Area of Science:

• Genetics
• Metabolic Disorders
• Cardiology

Background:

• Primary systemic carnitine deficiency results from mutations in the SLC22A5 gene, often presenting in early childhood with metabolic or cardiac symptoms.
• Carnitine uptake defect (CUD) affects cellular energy production, impacting organs with high energy demands like the heart and muscles.

Purpose of the Study:

• To identify the genetic cause of carnitine uptake defect in a family with hypertrophic cardiomyopathy and dysmorphic features.
• To characterize a novel mutation in the SLC22A5 gene and its association with clinical manifestations.

Main Methods:

• Tandem mass spectrometry (MS) was used to diagnose carnitine uptake defect.
• Exome sequencing of the SLC22A5 gene identified mutations.
• Array comparative genomic hybridization (array-CGH) was performed to investigate dysmorphic features.

Main Results:

• Tandem MS confirmed carnitine uptake defect in affected siblings.
• A novel homozygous mutation (c.1427T>G → p.Leu476Arg) in the SLC22A5 gene was identified in the affected siblings.
• Array-CGH revealed copy number variations but did not pinpoint the cause of dysmorphic features, suggesting the novel mutation may also contribute.

Conclusions:

• A novel SLC22A5 mutation is associated with primary systemic carnitine deficiency, hypertrophic cardiomyopathy, and potentially dysmorphic features.
• Early diagnosis and genetic identification are crucial for managing carnitine uptake defects.
• This case highlights the genetic heterogeneity and diverse clinical spectrum of SLC22A5-related disorders.