Intellectual disability syndromic and non-syndromic
Gene: DHTKD1

DHTKD1 (dehydrogenase E1 and transketolase domain containing 1)
EnsemblGeneIds (GRCh38): ENSG00000181192
EnsemblGeneIds (GRCh37): ENSG00000181192
OMIM: 614984, Gene2Phenotype
DHTKD1 is in 6 panels

1 review

Sumudu Perera (Royal Melbourne Hospital)

I don't know

Recent review: "The clinical presentation of AMOXAD can include developmental delay and seizures, but some individuals may be asymptomatic, leading to controversy regarding its clinical relevance" (Update current understanding of neurometabolic disorders related to lysine metabolism - Chang, PMID: 37499576)

Danhauser et al. (2012) (PMID: 23141293): "Over 20 individuals with this metabolic disease (2-aminoadipic 2-oxoadipic aciduria) are known. More than half of them are asymptomatic, whereas others have developed mild to severe intellectual disability, muscular hypotonia, developmental delay, ataxia, and epilepsy." (as reported from PMID: 1112064, 6434826).
* Further additional 2 patients reported by Danhauser et al; Their first patient had moderately delayed psychomotor development (sitting alone at 10 months and walking alone at 25 months) in infancy, which was improved with physiotherapy and occupational therapy. At the age of 8 testing showed an IQ of 117; at age 11 she was diagnosed with ADHD; and at 14 years of age she was in good health, attending regular school, and following a normal diet with a normal neurologic examination. Their second patient, with microcephaly, mild motor developmental delay (sitting alone at age 9 months and walking alone at the age 22 months), and prominent speech delay in early childhood. Her IQ was 87.
*Note these were retrospective cohorts; old study

Older papers regarding 2-aminoadipic 2-oxoadipic aciduria:
1. Fischer et al (1974) (PMID: 4442872): "2 brothers, aged 9 and 10 years. They attributed it to a defect in lysine metabolism. One had slight mental retardation (IQ 86), but the authors doubted a relation to the metabolic variant."
2. Lormans and Lowenthal (1974) (PMID: 4430147): "6-year-old boy with mental retardation"

Of note:
- Autosomal Dominant neuropathy - Charcot-Marie-Tooth disease, axonal, type 2Q, MIM#615025
- Autosomal recessive: 2-aminoadipic 2-oxoadipic aciduria MIM#204750
Created: 30 Aug 2024, 12:37 a.m. | Last Modified: 30 Aug 2024, 12:37 a.m.

Panel Version: 0.6123

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
2-aminoadipic 2-oxoadipic aciduria MIM#204750; Disorders of histidine, tryptophan or lysine metabolism

Publications

Created: 30 Aug 2024, 12:37 a.m.
Last Modified: 30 Aug 2024, 12:37 a.m.
Panel version: 0.6123

Details

Mode of Inheritance

BIALLELIC, autosomal or pseudoautosomal

Sources

Expert Review Amber
Genetic Health Queensland

Phenotypes

2-aminoadipic 2-oxoadipic aciduria MIM#204750
Disorders of histidine, tryptophan or lysine metabolism

OMIM

614984

Clinvar variants

Variants in DHTKD1

Penetrance

None

Publications

Panels with this gene