From Genotype to Phenotype: Investigating SLC22A5 Variants and Their Significance in Carnitine Deficiency: A Systematic Review Study.
Level 4 - case-series / case-control
Systematic review summarizing observational case reports and series without randomized or controlled comparisons.
PubMed 42480505 · doi:10.1111/jcmm.71273
What was done
Authors systematically searched PubMed for studies reporting genetic, biochemical, and clinical data regarding *SLC22A5* mutations in primary carnitine deficiency (PCD). Identified variants were classified according to ACMG guidelines and CADD computational scoring, followed by descriptive synthesis to assess genotype-phenotype correlations, particularly focusing on cardiomyopathy.
What was found
Missense mutations accounted for approximately 80% of reported cases, followed by deletions (12.7%), with other variant types being rare. By ACMG criteria, ~72% of variants were pathogenic or likely pathogenic, ~24% were variants of uncertain significance (VUS), and benign variants were uncommon. Exons 1 and 8 had the highest mutation frequency, but Exons 5 and 6 had higher mean CADD scores. Nonsense variants demonstrated the highest pathogenicity and CADD scores, followed by frameshift and missense variants. Severe truncating mutations were associated with early-onset cardiomyopathy.
Why it matters
The findings map the mutational landscape of *SLC22A5*, identifying exons with high functional vulnerability and linking severe truncating variants to early-onset cardiac involvement in PCD.
Limits
The total number of included studies and patients is not stated in the abstract. The search was restricted to a single database (PubMed). Conclusions rely primarily on descriptive synthesis and in silico pathogenicity tools rather than prospective or functional experimental validation.
Cited by
- supports Carnitine deficiency is an inborn error of metabolism that can prevent individuals from achieving a low Glucose Ketone Index without carnitine supplementation.