Novel heterozygous compound TRMT5 mutations associated with combined oxidative phosphorylation deficiency 26 in a Chinese family: a case report

Shuiyan Wu,Hongmei Chen,Saihu Huang,Weixi Li,Daoping Yang,Zhenjiang Bai,Ying Li,Haitao Lv,Ying Liu

doi:10.1186/s12887-022-03138-z

Abstract

BackgroundCombined oxidative phosphorylation deficiency 26 (COXPD26) is an autosomal recessive disorder characterized by early onset, developmental delay, gastrointestinal dysfunction, shortness of breath, exercise intolerance, hypotonia and muscle weakness, neuropathy, and spastic diplegia. This disease is considered to be caused by compound heterozygous mutations in the TRMT5 gene.Case presentationIn this study, we report a female child with COXPD26 manifesting as shortness of breath, gastrointestinal dysmotility, severe developmental delay, muscle hypotonia and weakness, exercise intolerance, renal and hepatic defects, and recurrent seizures with spastic diplegia. Interestingly, the hepatic feature was first observed in a COXPD26 patient. Medical exome sequencing with high coverage depth was employed to identify potential genetic variants in the patient. Novel compound heterozygous mutations of the TRMT5 gene were detected, which were c.881A>C (p.E294A) from her mother and c.1218G>C (p.Q406H) and c.1481C>T (p.T494M) from her father.ConclusionThe newly emerged clinical features and mutations of this patient provide useful information for further exploration of genotype–phenotype correlations in COXPD26.

Highlights

Combined oxidative phosphorylation deficiency 26 (COXPD26) is an autosomal recessive disorder characterized by early onset, developmental delay, gastrointestinal dysfunction, shortness of breath, exercise intolerance, hypotonia and muscle weakness, neuropathy, and spastic diplegia
In humans, when tRNA-N1 methyltransferase 5 (TRMT5) is transported into mitochondria, it methylates the tRNAs that are encoded by mitochondrial DNA [11]
We report a female patient with clinical features similar to previous cases of COXPD26 and a novel compound heterozygous mutation of TRMT5

Summary

Introduction

Combined oxidative phosphorylation deficiency 26 (COXPD26) is an autosomal recessive disorder characterized by early onset, developmental delay, gastrointestinal dysfunction, shortness of breath, exercise intolerance, hypotonia and muscle weakness, neuropathy, and spastic diplegia. Background Combined oxidative phosphorylation deficiency 26 (COXPD26; MIM #616539), which includes developmental delay, shortness of breath, exercise intolerance, spasticity hyporeflexia, and hypotonia leading to the patient being unable to sit, stand, or walk without support, and Powell et al reported a woman (the same case Haller et al reported) and a 7-year-old boy, both of whom showed muscle weakness, exercise intolerance, neuropathy, gastrointestinal problems, spasticity with hyperreflexia, increased serum lactate levels, and decreased activity of mitochondrial complex IV.

Results

Conclusion