Retinal Structure in Cobalamin C Disease: Mechanistic and Therapeutic Implications.

[homocystinuria without methylmalonic aciduria]

Abstract Purpose : To describe the retinal structure in a patient with cobalamin C (cblC ) disease . Methods : A 13 -year -old male patient diagnosed with cblC disease during a perinatal metabolic screening prompted by jaundice and hypotony underwent ophthalmic examinations , electroretinography (ERG ) and spectral domain optical coherence tomography (SD -OCT ). Results : The patient carried a homozygous (c .271 dupA ) mutation in the methylmalonic aciduria and homocystinuria type C (MMACHC ) gene . At age 3 months he had a normal eye exam . A pigmentary maculopathy progressed to chorioretinal atrophy from 5 -10 months . ERG at 7 months was normal . A nystagmus remained stable since the age of 2 years . At age 13 , visual acuity was 20 /250 (right eye ) and 20 /400 (left eye ), with a +5 .00 D correction , a level of vision maintained since first measurable at age 5 years . SD -OCT showed bilateral macular coloboma -like lesions ; there was also a thickened surface layer with ganglion cell layer thinning . Photoreceptor outer segment loss and thinning of the outer nuclear layer (ONL ) transitioned to regions with no discernible ONL with a delaminated , thickened , inner retina . Conclusions : A thick surface layer near the optic nerve resembling an immature retina and an initially normal macula that rapidly developed coloboma -like lesions suggest there may be an interference with retinal /foveal development in cblC , a mechanism of maculopathy that may be shared by other early onset retinal degenerations . Photoreceptor loss and inner retinal remodeling confirm associated photoreceptor degeneration .