Genotype and clinical phenotype of monocarboxylate transporter 1 deficiency in three Palestinian children: Report of two novel variants in the SLC16A1 Gene.

Abstract

Monocarboxylate transporter 1 (MCT1) deficiency (OMIM# 616095), caused by variants in the SLC16A1 gene (OMIM# 600682), is responsible for the transport of monocarboxylates across the plasma membrane. This condition is recognized as a rare genetic cause of impaired ketone body utilization in extrahepatic tissues, resulting in recurrent ketoacidosis triggered by fasting and infection. To date, only 17 patients with this disorder have been identified. Individuals with homozygous variants typically present at a younger age, exhibit developmental delays, and experience more severe ketoacidosis. We describe the genotype and clinical phenotype of three Palestinian children with MCT1 deficiency from two unrelated families. In an extended consanguineous family (Family A), whole exome sequencing identified a novel homozygous missense variant, SLC16A1_p.Gly25Val, in patient 1. Patient 2 was homozygous for the same variant. In unrelated family B, exome sequencing of patient 3 revealed another novel homozygous missense variant, SLC16A1_p.Leu403Phe. The clinical phenotypes and biochemical abnormalities were similar across all three patients, characterized by acute recurrent vomiting, severe dehydration, metabolic acidosis, and hyperuricemia. MCT1 deficiency should be considered in infants and children who experience recurrent ketoacidosis. We report two novel homozygous variants in the SLC16A1 gene, further expanding the genotype–phenotype spectrum of this rare disorder