Multiple sclerosis and intracellular cobalamin defect (MMACHC/PRDX1) comorbidity in a young male.

Abstract

BACKGROUND:

Methylmalonic acidaemia with homocystinuria type C (cblC defect) is an inherited error of cobalamin metabolism. Cobalamin deficient processing results in high levels of methylmalonic acid and homocysteine. The latter is considered to be a risk factor for multiple sclerosis (MS). We report on the first case of a patient with comorbid cblC defect and MS.

CASE REPORT:

This young male presented at the age of 14 with a relapsing-remitting neurological disorder associated with imaging alterations suggestive of MS. Treatment resulted in a partial clinical improvement with vanishing of white matter lesions. Later on, the emergence of unexpected clinical features led to a metabolic work-up, revealing a cobalamin intracellular defect. Genetic analysis disclosed a single variant in MMACHC (c.482G > A; p.Arg161Gln) and another splicing variant in PRDX1 (c.1-515G > T) that cause the silencing of the wild-type MMACHC allele, so confirming the diagnosis of cblC defect. Although cblC treatment was effective, when 17-year-old he experienced a relapse of neurological symptoms. Further imaging and laboratory studies eventually supported the diagnosis of MS.

DISCUSSION:

While the comorbid association of MS and cblC in our patient may remain anecdotic, we suggest measuring Hcy and MMA levels in young patients with a relapsing-remitting demyelinating disorder, in order not to miss a cblC defect, that requires a specific and effective treatment.

• Authors: Luca Pollini, Manuela Tolve, Francesca Nardecchia, Serena Galosi, Claudia Carducci, Emanuele di Carlo, Carla Carducci, Vincenzo Leuzzi
• Journal: Molecular genetics and metabolism reports (Mol Genet Metab Rep) Vol. 22 Pg. 100560 (Mar 2020) ISSN: 2214-4269 [Print] United States
• PMID: 32099815 (Publication Type: Case Reports)
• Copyright: © 2019 The Authors.