Childhood onset dystonia, chorea or related movement disorder

Gene: OGDH

Green List (high evidence)

Comment on list classification: There is sufficient evidence available (four unrelated families) for the association of biallelic OGDH variants with childhood-onset dystonia. Hence, this gene can be promoted to green rating in the next GMS update.

Created: 29 Jul 2026, 7:50 p.m. | Last Modified: 29 Jul 2026, 7:53 p.m.

Panel Version: 8.12

PMID:32383294 (2021) reported two siblings identified with a homozygous missense variant c.959A>G (p.Asn320Ser) in the OGDH gene. These individuals presented with global developmental delay, elevated lactate, ataxia and seizure.

PMID:36520152 (2023) reported four unrelated individuals with 3 different homozygous OGDH variants and presenting with a neurodevelopmental disorder characterised by global developmental delay, movement disorder, and metabolic abnormalities.

There are six patients from five families reported in total with four different homozygous variants in OGDH gene and with a neurodevelopmental disorder with metabolic and movement abnormalities. Age of onset of the disease ranged from 6 weeks of age to 3 years old. All described individuals shared the clinical features of global developmental delay, hypotonia, metabolic acidosis and increased serum lactate. Additional shared clinical features included dystonia (5/6), microcephaly (3/4), abnormal nasal bridge morphology (3/6), hyperammonemia (3/6), hyperglutaminemia (3/3 who were tested), and elevated alpha-ketoglutarate in the urine (2/4 who were tested).

This gene has been associated with relevant phenotype in OMIM (MIM #203740, last accessed 29 July 2026) and in Gene2Phenotype (with 'moderate' rating on the DD panel). This gene has also been associated with mitochondrial disease (MONDO:0044970) with 'Definitive' rating by the Mitochondrial Diseases GCEP in ClinGen (https://search.clinicalgenome.org/CCID:009318)
Sources: Literature

Created: 29 Jul 2026, 7:47 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Oxoglutarate dehydrogenase deficiency, OMIM:203740; oxoglutaricaciduria, MONDO:0008759

Publications

• 32383294
• 36520152