Markedly Elevated Citrulline in a Neonate: Citrin Deficiency due to a Previously Unreported Solute Carrier Family 25 Member 13 Variant.

Background: Citrin deficiency (CD) is an autosomal recessive metabolic disorder affecting the urea cycle and energy production. Diagnosis involves measuring ammonia and amino acid levels (eg: citrulline), with confirmation through solute carrier family 25 member 13 (SLC25A13) gene mutation analysis. Herein, we present a case report of a variant in the SLC25A13 gene that has not been previously reported in the literature.

Case report and results: The subject was a full-term Hispanic girl infant who was provisionally diagnosed with amino aciduria/urea cycle disorder with citrullinemia of unidentified type based on the second newborn screen performed at the 10th day of life. Sequence analysis and deletion/duplication testing using a panel consisting of 5 genes pertaining to citrullinemia revealed the patient carried a frameshift variant in the SLC25A13 gene (c.429_430del; pArg144fs) consistent with elevated citrulline results. The variant is not found in population databases (gnomAD). While ClinVar has only one entry for this variant (Variation ID: 1076508) and classifies it as pathogenic/likely pathogenic, no case report association exists between this variant and citrullinemia/CD or any SLC25A13-related conditions.

Conclusion: This case study expands the CD variant spectrum and describes a frameshift variant in the SLC25A13 gene in a patient linked to pathology. The finding emphasizes the importance of integrating clinical features with biochemical and genetic analysis to better understand genotype-phenotype correlations in CD and improve management strategies.