Novel MTR compound-heterozygous mutations in a Chinese girl with HHcy due to methionine synthase deficiency, cblG: a case report

Abstract Background The methylcobalamin deficiency G (cblG) disorder, a rare autosomal recessive disease, is attributed to mutations in the MTR gene, resulting in heightened homocysteine levels and reduced methionine and megaloblastic anemia levels. This disease is predominantly diagnosed using MTR gene variation analysis. Case presentation Herein, we report the case of a 2.1-month-old Chinese girl with the cblG disorder with poor feeding, failure to thrive, and pancytopenia, esotropia, ocular nystagmus, and hypotonia. However, in order to determine the possible genetic cause of the disease, whole-exome sequencing was adopted and detected compound-heterozygous mutations in MTR gene. One was splicing site mutation c.1812 + 3A > G and the other was missense mutation c.2405G > A (p.A802G), which were likely disease-causing mutations (DM). Variant c.1812 + 3A > G has not been reported before in the literature. Conclusion Our data elucidated the genetic etiology of the patient and enriched the known spectrum of mutations in the MTR gene worldwide, offering exhaustive and invaluable insights for early diagnosis and appropriate medication of the cblG disorder.