JIMD Reports, Volume 25

Ashlee R. Stiles, Leah Venturoni, Grace Mucci, Naser Elbalalesy, Michael Woontner, Stephen Goodman, Jose E. Abdenur, Stiles, Ashlee R., Venturoni, Leah, Mucci, Grace, Elbalalesy, Naser, Woontner, Michael, Goodman, Stephen, Abdenur, Jose E.

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.