Ocular manifestations in patients with inborn errors of intracellular cobalamin metabolism: a systematic review

source extracted confidence: high 2026-04-09
#amino-acid-metabolism-inborn-errors #homocystinuria #humans #macular-degeneration #methylmalonic-acid

Ocular manifestations in patients with inborn errors of intracellular cobalamin metabolism: a systematic review

Matmat et al., 2022 | Hum Genet | Systematic Review

Citation

Matmat Karim, Guéant-Rodriguez Rosa-Maria, ... Conart Jean-Baptiste. Ocular manifestations in patients with inborn errors of intracellular cobalamin metabolism: a systematic review. Hum Genet. 2022-Jul;141(7):1239-1251. doi:10.1007/s00439-021-02350-8

Abstract

Inherited disorders of cobalamin (cbl) metabolism (cblA-J) result in accumulation of methylmalonic acid (MMA) and/or homocystinuria (HCU). Clinical presentation includes ophthalmological manifestations related to retina, optic nerve and posterior visual alterations, mainly reported in cblC and sporadically in other cbl inborn errors.We searched MEDLINE EMBASE and Cochrane Library, and analyzed articles reporting ocular manifestations in cbl inborn errors. Out of 166 studies a total of 52 studies reporting 163 cbl and 24 mut cases were included. Ocular manifestations were found in all cbl defects except for cblB and cblD-MMA; cblC was the most frequent disorder affecting 137 (84.0%) patients. The c.271dupA was the most common pathogenic variant, accounting for 70/105 (66.7%) cases. One hundred and thirty-seven out of 154 (88.9%) patients presented with early-onset disease (0-12 months). Nystagmus and strabismus were observed in all groups with the exception of MMA patients while maculopathy and peripheral retinal degeneration were almost exclusively found in MMA-HCU patients. Optic nerve damage ranging from mild temporal disc pallor to complete atrophy was prevalent in MMA-HCU.and MMA groups. Nystagmus was frequent in early-onset patients. Retinal and macular degeneration worsened despite early treatment and stabilized systemic function in these patients. The functional prognosis remains poor with final visual acuity < 20/200 in 55.6% (25/45) of cases. In conclusion, the spectrum of eye disease in Cbl patients depends on metabolic severity and age of onset. The development of visual manifestations over time despite early metabolic treatment point out the need for specific innovative therapies.

Key Findings

The development of visual manifestations over time despite early metabolic treatment point out the need for specific innovative therapies.

Outcomes Measured

  • Requires manual extraction

Population

Field Value
Population See abstract
Sample Size 166
Age Range See abstract
Condition See abstract

MeSH Terms

  • Amino Acid Metabolism, Inborn Errors
  • Homocystinuria
  • Humans
  • Macular Degeneration
  • Methylmalonic Acid
  • Mutation
  • Retina
  • Retinal Degeneration
  • Vitamin B 12

Evidence Classification

  • Level: Systematic Review
  • Publication Types: Journal Article, Systematic Review
  • Vertical: vitamin-b12

Provenance

Source extracted via PubMed E-utilities API on 2026-04-09