Journal of Pediatric Neurology
DOI: 10.1055/s-0040-1712174
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Infantile onset Encephalomyopathy, Heart Block, and Sensorineural Hearing Loss: RMND1-Associated Mitochondrial Disease

Madhu Nagappa
1  Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
V.P. Vandana
3  Departments of Speech Pathology and Audiology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
Shwetha Chiplunkar
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
4  Departments of Clinical Neurosciences, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
Periyasamy Govindaraj
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
5  Departments of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
6  Institute of Bioinformatics, International Tech Park, Bangalore, Karnataka, India
7  Manipal Academy of Higher Education, Manipal, Karnataka, India
,
J.N. Jessiena Ponmalar
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
Narayanappa Gayathri
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
5  Departments of Neuropathology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
Sanjib Sinha
1  Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
Arun B. Taly
1  Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
,
1  Departments of Neurology, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
2  Neuromuscular Lab, Neurobiology Research Center, National Institute of Mental Health and Neurosciences (NIMHANS), Bangalore, Karnataka, India
› Author Affiliations
Funding This study was supported by a grant from the Indian Council of Medical Research to B.P.S. (grant no.: 54/9/2012-HUM-BMS).
Further Information

Publication History

31 December 2019

19 April 2020

Publication Date:
26 May 2020 (online)

Abstract

Mutations in RMND1 (required for mitotic division-1) has been associated with infantile onset mitochondrial disease and combined oxidation phosphorylation deficiency. This report describes a girl child of Indian origin with RMND1-associated mitochondrial disease. This 13-month-old girl, born to consanguineous parents presented with gradual loss of acquired milestones and recurrent vomiting from 5 months of age. She experienced failure to thrive, profound hypotonia, areflexia, and sensorineural deafness. Evaluation showed elevated serum lactate and complete heart block. Audiological evaluation done at 6 and 13 months of age revealed bilateral A type tympanogram, bilateral absent stapedial reflexes, absent otoacoustic emissions (OAE), and absent brainstem auditory evoked responses suggestive of bilateral profound sensorineural hearing loss. Muscle biopsy revealed evidence of ragged red fibers, ragged blue fibers, and Cytochrome coxidase (COX) deficient fibers on histochemistry and multiple complex deficiency on spectrophotometry. Exome sequencing revealed homozygous stop-loss variation, c.1349G > C, in exon 12 of RMDN1 resulting in substitution of amino acid serine for stop codon at position 450 and subsequent elongation of the protein by 31 amino acids (p.Ter450SerextTer31) which was verified by Sanger's sequencing. This report further strengthen the phenotype genotype correlations in RMND1-associated mitochondrial disease, especially the occurrence of the reported variation in South Asian patients. In addition, familiarity with the phenotype may help the physician to do targeted metabolic testing and facilitate appropriate early interventions.

Authors' Contributions

B.P.S. and A.B.T. contributed in conceptualization and designing, as well as acquisition, analysis, and interpretation of data. M.N. performed the literature search and wrote the manuscript. A.B.T., B.P.S., M.N., S.C., and S.S. performed as a clinical team involved in the evaluation, management, and follow-up of the patient. N.G. was involved in the acquisition and interpretation of histopathological data. J.N.J.P. contributed in acquisition and interpretation of respiratory chain assays. S.C. and P.G. performed interpretation of genetic data. V.P.V. contributed with acquisition and interpretation of audiological findings. All authors reviewed and approved the final manuscript.