CISD2 and Leber hereditary optic neuropathy: In addition, the phenotype of TRMA syndrome is highly overlapping with Wolfram syndrome (caused by variants in CISD2 or WFS1 gene), which is mainly manifested by diabetes, optic atrophy and deafness.20, 21, 22 These results indicate that identifying and accurately diagnosing TRMA syndrome in the early stage may face some challenges, therefore, introducing genetic test approaches can effectively improve diagnostic efficiency.