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

Luca Pollini; Manuela Tolve; Francesca Nardecchia; Serena Galosi; Claudia Carducci; Emanuele di Carlo; Carla Carducci; Vincenzo Leuzzi

doi:10.1016/j.ymgmr.2019.100560

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

Mol Genet Metab Rep. 2020 Jan 7:22:100560. doi: 10.1016/j.ymgmr.2019.100560. eCollection 2020 Mar.

Authors

Luca Pollini^{1

2}, Manuela Tolve^{1

2}, Francesca Nardecchia^{1

2}, Serena Galosi^{1

2}, Claudia Carducci^{1

2}, Emanuele di Carlo^{1

2}, Carla Carducci^{1

2}, Vincenzo Leuzzi^{1

2}

Affiliations

¹ Sapienza University of Rome, Department of Human Neuroscience, Rome, Italy.
² Sapienza University of Rome, Department of Experimental Medicine, Rome, Italy.

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.

Keywords: MMACHC; Multiple sclerosis; PRDX1; cblC; cblC, cobalamin deficiency type C; homocysteine, hcy; magnetic resonance imaging, MRI; methylmalonic acid, MMA; multiple sclerosis, MS.

Publication types

Case Reports