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

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.

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.

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.