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Journal of Pediatric Neurology 2023; 21(05): 408-410
DOI: 10.1055/s-0042-1758470
Letter to the Editor

Paroxysmal Dystonia in a Child with Enoyl-CoA Hydratase Short-Chain 1 (ECHS1) Mutations

Akshata Huddar
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Periyasamy Govindaraj
2   Centre for DNA Fingerprinting and Diagnostics, Hyderabad, Telangana, India
,
Shwetha Chiplunkar
3   Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
4   Clinical Neurosciences, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Madhu Nagappa
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3   Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Arun B. Taly
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3   Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
,
Bindu Parayil Sankaran 
1   Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
3   Neuromuscular Laboratory, Neurobiology Research Centre, National Institute of Mental Health and Neurosciences, Bengaluru, Karnataka, India
5   The Children's Hospital at Westmead Clinical School, Sydney Medical School, Faculty of Medicine and Health, The University of Sydney, Sydney, Australia
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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.

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Fig. 1 Magnetic resonance imaging of the brain: axial sections show symmetrical hyperintensity (arrow) of bilateral globus pallidus ([A] T2-weighted images) with restricted diffusion ([B] diffusion-weighted image and [C] apparent diffusion coefficient image).

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.

Zoom Image
Fig. 2 The representative sequence electropherogram of ECHS1 variations. (A) The upper panel shows (arrow) the wild-type nucleotide “G,” while the lower panel showing heterozygous “G/A” for the variation c.463G/A. (B) The upper panel shows (arrow) the wild-type nucleotide “G,” while the lower panel showing heterozygous “G” deletion for the variation c.619 + 1delG.

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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