title: Genetic basis of alpha-aminoadipic and alpha-ketoadipic aciduria.
abstract: Alpha-aminoadipic and alpha-ketoadipic aciduria is an autosomal recessive inborn error of lysine, hydroxylysine, and tryptophan degradation. To date, DHTKD1 mutations have been reported in two alpha-aminoadipic and alpha-ketoadipic aciduria patients. We have now sequenced DHTKD1 in nine patients diagnosed with alpha-aminoadipic and alpha-ketoadipic aciduria as well as one patient with isolated alpha-aminoadipic aciduria, and identified causal mutations in eight. We report nine novel mutations, including three missense mutations, two nonsense mutations, two splice donor mutations, one duplication, and one deletion and insertion. Two missense mutations, one of which was reported before, were observed in the majority of cases. The clinical presentation of this group of patients was inhomogeneous. Our results confirm that alpha-aminoadipic and alpha-ketoadipic aciduria is caused by mutations in DHTKD1, and further establish that DHTKD1 encodes the E1 subunit of the alpha-ketoadipic acid dehydrogenase complex.
authors: Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, 1425 Madison Avenue, Box 1498, New York, NY, 10029, USA.
authors: Jacob
authors: J
authors: Hagen
authors: Heleen
authors: H
authors: te Brinke
authors: Ronald J A
authors: RJ
authors: Wanders
authors: Alida C
authors: AC
authors: Knegt
authors: Esmee
authors: E
authors: Oussoren
authors: A Jeannette M
authors: AJ
authors: Hoogeboom
authors: George J G
authors: GJ
authors: Ruijter
authors: Daniel
authors: D
authors: Becker
authors: Karl Otfried
authors: KO
authors: Schwab
authors: Ingo
authors: I
authors: Franke
authors: Marinus
authors: M
authors: Duran
authors: Hans R
authors: HR
authors: Waterham
authors: Jörn Oliver
authors: JO
authors: Sass
authors: Sander M
authors: SM
authors: Houten
mesh_terms: D015074:2-Aminoadipic Acid / Q000378:metabolism* / Q000652:urine; D000272:Adipates / Q000378:metabolism* / Q000652:urine; D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007655:Ketoglutarate Dehydrogenase Complex; D007658:Ketone Oxidoreductases / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D008297:Male; D055815:Young Adult
chemical_list: D000272:Adipates; D015074:2-Aminoadipic Acid; C001918:alpha-ketoadipic acid; D007658:Ketone Oxidoreductases; C578281:DHTKD1 protein, human; D007655:Ketoglutarate Dehydrogenase Complex