Mitochondrial disease

Gene: WARS2

Green List (high evidence)

Childhood-onset parkinsonism-dystonia-3 (PKDYS3) is an autosomal recessive neurodegenerative disorder with onset in infancy or early childhood. Affected individuals present with progressive movement abnormalities, including parkinsonism with tremor, dystonia, myoclonus ataxia, and hyperkinetic movements such as ballismus. The parkinsonism features may be responsive to treatment with levodopa, although many patients develop levodopa-induced dyskinesia. Some patients may have mild cognitive impairment or psychiatric disturbances. 8 individuals from 4 families reported.

NEMMLAS is an autosomal recessive multisystemic disorder characterized by delayed psychomotor development, intellectual disability, and abnormal motor function, including hypotonia, dystonia, ataxia, and spasticity. Patient tissues may show deficiencies in one or more of the mitochondrial oxidative phosphorylation (OXPHOS) enzymes, but this is not a constant finding. 12 individuals from 8 unrelated families reported.

It is unclear whether these are two distinct disorders or whether they represent a spectrum of severity for a single condition.

Created: 20 Feb 2022, 6:58 a.m. | Last Modified: 20 Feb 2022, 6:58 a.m.

Panel Version: 0.11005

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Parkinsonism-dystonia 3, childhood-onset, MIM# 619738; Neurodevelopmental disorder, mitochondrial, with abnormal movements and lactic acidosis, with or without seizures, MIM# 617710

Publications

• 29120065
• 31970218
• 34890876
• 28236339
• 28650581
• 28905505
• 30920170