# Retinal Changes in Early-Onset cblC Methylmalonic Acidemia Identified Through Expanded Newborn Screening: Highlights from a Case Study and Literature Review

## TL;DR

This case study shows that retinal degeneration can occur in newborns with cblC methylmalonic acidemia, even with early treatment, highlighting the need for immediate therapy and close eye monitoring.

## Contribution

The study emphasizes the importance of early ophthalmological monitoring in cblC patients to detect retinal changes before visual symptoms appear.

## Key findings

- Retinal degeneration was detected at 3 months in a newborn with cblC despite early treatment.
- Bull’s eye maculopathy and reduced ERG amplitudes were observed at 7 months.
- Visual field testing showed no abnormalities despite retinal changes.

## Abstract

Background: Methylmalonic acidemia combined with homocystinuria (cblC) can lead to infantile maculopathy. Although significant visual deterioration is commonly reported in early-onset cblC, we found poor awareness regarding formal assessments of ocular complications, especially in newborns, and of how these complications relate to the timing of therapy initiation. In this work, we present our experience and perform a literature review. Methods: We performed sequential fundus examinations, optical coherence tomography (OCT) and full-field electroretinography (ERG) under sedation following detection of signs of retinal degeneration. We also assessed visual fields using kinetic attraction perimetry. Results: We report a newborn who was referred on the eighth day of life, following a diagnosis of cblC through newborn screening (NBS), and who began treatment that same day. Close monitoring of retinal changes through fundus examinations allowed the detection of signs of retinal degeneration at 3 months, which progressed when checked at 5 months. At 7 months, OCT showed retinal thinning with the appearance of bull’s eye maculopathy in the corresponding region on fundoscopy; ERG revealed a reduction in the amplitude of both scotopic and photopic components, whereas kinetic attraction perimetry showed no abnormalities. Genetic investigation confirmed the disease, compound heterozygous for a nonsense variant in MMACHC and a splicing one in PRDX1. Conclusions: In cblC, retinal degeneration occurs in the first months of life despite timely treatment and adequate biochemical control, and it may manifest before any signs of visual deprivation appear. However, there is an early, narrow window during which therapy may slow down retinal degeneration enough to prevent sensory nystagmus. We recommend initiating therapy immediately after biochemical diagnosis, along with close ophthalmological monitoring, before the appearance of any signs.