TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels

Ewout Muylle; Huafang Jiang; Christin Johnsen; Seul Kee Byeon; Wasantha Ranatunga; Kishore Garapati; Roman M Zenka; Graeme Preston; Akhilesh Pandey; Tamas Kozicz; Fang Fang; Eva Morava

doi:10.1002/jimd.12550

TRIT1 defect leads to a recognizable phenotype of myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and normal lactate levels

J Inherit Metab Dis. 2022 Nov;45(6):1039-1047. doi: 10.1002/jimd.12550. Epub 2022 Sep 21.

Authors

Ewout Muylle¹, Huafang Jiang², Christin Johnsen¹, Seul Kee Byeon³, Wasantha Ranatunga¹, Kishore Garapati^{3

4

5}, Roman M Zenka³, Graeme Preston¹, Akhilesh Pandey³, Tamas Kozicz^{1

3}, Fang Fang², Eva Morava^{1

3

6

7}

Affiliations

¹ Department of Clinical Genomics, Mayo Clinic, Rochester, Minnesota, USA.
² Department of Neurology, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing, China.
³ Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota, USA.
⁴ Institute of Bioinformatics, International Technology Park, Bangalore, Karnataka, India.
⁵ Manipal Academy of Higher Education, Manipal, Karnataka, India.
⁶ Department of Medical Genetics, University of Pecs Medical School, Pecs, Hungary.
⁷ Department of Biophysics, University of Pecs Medical School, Pecs, Hungary.

Abstract

TRIT1 defect is a rare, autosomal-recessive disorder of transcription, initially described as a condition with developmental delay, myoclonic seizures, and abnormal mitochondrial function. Currently, only 13 patients have been reported. We reviewed the genetic, clinical, and metabolic aspects of the disease in all known patients, including two novel, unrelated TRIT1 cases with abnormalities in oxidative phosphorylation complexes I and IV in fibroblasts. Taken together the features of all 15 patients, TRIT1 defect could be identified as a potentially recognizable syndrome including myoclonic epilepsy, speech delay, strabismus, progressive spasticity, and variable microcephaly, with normal lactate levels. Half of the patients had oxidative phosphorylation complex measurements and had multiple complex abnormalities.

Keywords: OXPHOS; lipidomics; mitochondrial tRNA; myoclonic seizures; spasticity.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Alkyl and Aryl Transferases* / genetics
Epilepsies, Myoclonic* / genetics
Humans
Lactates
Language Development Disorders*
Muscle Spasticity
Phenotype
Strabismus*

Substances

Lactates
TRIT1 protein, human
Alkyl and Aryl Transferases