Clinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin B12 metabolism: A meta-analysis

Cell Rep Med. 2022 Jul 19;3(7):100670. doi: 10.1016/j.xcrm.2022.100670. Epub 2022 Jun 27.

Abstract

Inherited disorders of B12 metabolism produce a broad spectrum of manifestations, with limited knowledge of the influence of age and the function of related genes. We report a meta-analysis on 824 patients with a genetically proven diagnosis of an inherited disorder of vitamin B12 metabolism. Gene clusters and age categories are associated with patients' manifestations. The "cytoplasmic transport" cluster is associated with neurological and ophthalmological manifestations, the "mitochondrion" cluster with hypotonia, acute metabolic decompensation, and death, and the "B12 availability" and "remethylation" clusters with anemia and cytopenia. Hypotonia, EEG abnormalities, nystagmus, and strabismus are predominant in the younger patients, while neurological manifestations, such as walking difficulties, peripheral neuropathy, pyramidal syndrome, cerebral atrophy, psychiatric disorders, and thromboembolic manifestations, are predominant in the older patients. These results should prompt systematic checking of markers of vitamin B12 status, including homocysteine and methylmalonic acid, when usual causes of these manifestations are discarded in adult patients.

Keywords: MMACHC; cobalamin; inherited metabolic disorders; methionine synthase; methylmalonyl-CoA mutase; vitamin B(12); vitamin B(12) deficiency.

Publication types

  • Case Reports
  • Meta-Analysis
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Methylmalonic Acid
  • Muscle Hypotonia / complications
  • Vitamin B 12 Deficiency* / genetics
  • Vitamin B 12* / metabolism
  • Vitamins

Substances

  • Vitamins
  • Methylmalonic Acid
  • Vitamin B 12