Ophthalmic Genet. 2025 Nov 18:1-4. doi: 10.1080/13816810.2025.2590165. Online ahead of print.
ABSTRACT
BACKGROUND: Among the genes implicated in inherited retinal degenerations (IRDs), disease-causing variants in IDH3A have recently been reported, although they remain exceedingly rare. In some cases, these variants are associated with macular pseudocoloboma. IDH3A encodes the alpha subunit of the mitochondrial NAD+-dependent isocitrate dehydrogenase 3 (IDH3) complex, a key enzyme in the tricarboxylic acid (TCA) cycle.
METHODS: Ophthalmic examination and whole-exome sequencing.
RESULTS: We report the case of a 2-month-old female infant presenting with bilateral macular pseudocoloboma. Clinical examination showed age-appropriate visual behavior. Fundoscopy revealed well-defined atrophic lesions in the macula, retinal pigment epithelium (RPE) changes and vascular narrowing in both eyes. Whole-exome sequencing revealed that the patient appears to be homozygous for the NM_005530.3(IDH3A):c.364G>A (p.Ala122Thr) variant.
CONCLUSION: To our knowledge, this is the youngest reported patient with IDH3A-associated retinal dystrophy presenting with macular pseudocoloboma and expands the phenotypic spectrum of this disease.
PMID:41250664 | DOI:10.1080/13816810.2025.2590165