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DOI: 10.1055/s-0042-1758470
Paroxysmal Dystonia in a Child with Enoyl-CoA Hydratase Short-Chain 1 (ECHS1) Mutations
A 2-year-old boy, born at term to healthy unrelated parents after an uncomplicated pregnancy, presented with recurrent daily episodes of dystonia (3-4/day) since 1-and-half years of age. Episodes consisted of generalized dystonia precipitated by fever, walking or other minor motor activity, occurring multiple times per day, lasting for about 30 to 60 minutes, without any diurnal variation. The patient had normal development. Neurological examination in between the episodes revealed normal cranial nerves, power, tone, and reflexes . Before presenting to us, he received levodopa and acetazolamide for 6 months without benefit.
Laboratory evaluation revealed elevated serum lactate (24.3 and 29, reference: 4.5–20 mg/dL) and ammonia (75 and 208, reference: 16–60 μmol/L). Hematology, renal, hepatic, and thyroid function tests, creatine kinase, copper, calcium, magnesium, plasma amino acids and acylcarnitine, and urinary organic acid profile were normal. Magnetic resonance imaging of the brain demonstrated T2/fluid-attenuated inversion recovery hyperintensities in bilateral globus pallidus ([Fig. 1]). In combination with elevated lactate and bilateral symmetrical basal ganglia lesions, the clinical features raised suspicion for a mitochondrial disorder.
Patient underwent whole exome sequencing. This revealed compound heterozygous variants of uncertain significance in exon 4 of enoyl-CoA hydratase short-chain 1 (ECHS1); 5′ splice site variation, c.619 + 1delG, and a missense variation c.463G > A(p.Gly155Ser) ([Fig. 2]). Both parents were heterozygous for one of the two variants by segregation analysis. Both the variants were conserved across species. He was commenced on mitochondrial cocktail (carnitine 500 mg, coenzyme Q 30 mg, vitamin C 250 mg, biotin 10 mg, cyanocobalamin 300 µg, niacinamide 450 mg, pyridoxine 25 mg, riboflavin 100 mg, thiamine 100 mg daily).[1] At 1 month follow-up, parents reported a reduction in the frequency of the episodes to one to two times per week. There was probably also a reduction in severity as the dystonia involved only the lower limbs.
Ethical Approval
The parents provided consent for the publication of this manuscript. This study was approved by the Institutional Ethics Committee (No. NIMHANS/91st/2014).
Publication History
Received: 01 June 2022
Accepted: 20 September 2022
Article published online:
01 December 2022
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