New Cases of DHTKD1 Mutations in Patients with 2-Ketoadipic Aciduria

JIMD Rep. 2016:25:15-19. doi: 10.1007/8904_2015_462. Epub 2015 Jul 5.

Abstract

2-Ketoadipic aciduria (OMIM 204750), a defect in the catabolic pathway of tryptophan, lysine, and hydroxylysine, is characterized by elevations in 2-ketoadipic, 2-aminoadipic, and 2-hydroxyadipic acids. Patients with the aforementioned biochemical profile have been described with a wide range of clinical presentations, from early-onset developmental delay, epilepsy, ataxia, and microcephaly to completely normal. This broad range of phenotypes has led some to question whether 2-ketoadipic aciduria represents a true disease state or if the biochemical abnormalities found in these patients merely reflect an ascertainment bias. We present four additional individuals from two families, with 2-ketoadipic aciduria with compound heterozygous or homozygous mutations in DHTKD1, three of which remain asymptomatic.

Keywords: 2-Aminoadipic; 2-Ketoadipic aciduria; 2-Oxoadipic aciduria; DHTKD1; Hydroxylysine; Lysine; Organic acidemia; Tryptophan.