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.

Multiple sclerosis and intracellular cobalamin defect (MMACHC/PRDX1) comorbidity in a young male / Pollini, L.; Tolve, M.; Nardecchia, F.; Galosi, S.; Carducci, C.; di Carlo, E.; Carducci, C.; Leuzzi, V.. - In: MOLECULAR GENETICS AND METABOLISM REPORTS. - ISSN 2214-4269. - 22:(2020), p. 100560. [10.1016/j.ymgmr.2019.100560]

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

Pollini L.;Tolve M.;Nardecchia F.;Galosi S.;Carducci C.;Carducci C.;Leuzzi V.
2020

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.
2020
cblC; MMACHC; Multiple sclerosis; PRDX1
01 Pubblicazione su rivista::01a Articolo in rivista
Multiple sclerosis and intracellular cobalamin defect (MMACHC/PRDX1) comorbidity in a young male / Pollini, L.; Tolve, M.; Nardecchia, F.; Galosi, S.; Carducci, C.; di Carlo, E.; Carducci, C.; Leuzzi, V.. - In: MOLECULAR GENETICS AND METABOLISM REPORTS. - ISSN 2214-4269. - 22:(2020), p. 100560. [10.1016/j.ymgmr.2019.100560]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11573/1386553
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