Hereditary defect of cobalamin metabolism with adolescence onset resembling multiple sclerosis: 41-year follow up in two cases.

The cblC defect is the most common inborn error of cobalamin (Cbl) metabolism. Clinical severity and presentation of the cblC defect ranges from death to mild disability. Only 71 cases of late-onset cblC defect have been described in the literature. We provide the 41-year follow up of two siblings with a late-onset cblC defect, first described after initial diagnosis in 1996. While one of the siblings showed initial symptoms resembling multiple sclerosis with a good response to corticosteroids, the other sister showed only subclinical signs of the disease. The course of the first case was characterized by a severe deterioration and intensive-care therapy after respiratory failure. After diagnoses and Cbl treatment, the patient survived and showed a pronounced improvement of the symptoms. Both sisters have an active life and gave birth to healthy children. The reason for the initial improvement after corticosteroids could not be explained by the classical metabolic pathways of Cbl. Recent studies have suggested that Cbl plays an important role as a regulator of the balance between neurotrophic and neurotoxic factors in the central and peripheral nervous system (CNS and PNS). This first long-term follow up revealed that ultra-high-dose intramuscular Hydroxocobalamin (OH-Cbl) treatment can effectively protect patients from disease progression. It underlines the importance of diagnostic vigilance and laboratory work up even in cases without typical hematologic signs of Cbl deficiency. Cbl-related diseases are often a chameleon and must always be considered in the differential of demyelinating diseases of the PNS and CNS. The case supports the theory that it is not only the classical biochemical pathways that play a key role in Cbl deficiency, especially with regard to neurological symptoms.
Competing Interests: Conflict of interest statement: JM received travel grants from Biogen, his research is funded by the Klaus Tschira Foundation and Ruhr-University Bochum (FoRUM-Program); none related to this work. KS-K received travels grants for scientific meetings from Bayer Vital. KP received travel grants and speaker’s honoraria from Biogen, Bayer Schering, and Novartis. LK has received in the last 3 years and used exclusively for research support steering committee, advisory board, and consultancy fees (Actelion, Addex, Bayer HealthCare, Biogen, Biotica, Genzyme, Lilly, Merck, Mitsubishi, Novartis, Ono Pharma, Pfizer, Receptos, Sanofi, Santhera, Siemens, Teva, UCB, and XenoPort); speaker fees (Bayer HealthCare, Biogen, Merck, Novartis, Sanofi, Teva); support for educational activities (Bayer HealthCare, Biogen, CSL Behring, Genzyme, Merck, Novartis, Sanofi, Teva); royalties (Neurostatus); grants (Bayer HealthCare, Biogen, EU, Merck, Novartis, Roche Research Foundation, Swiss MS Society, Swiss National Research Foundation). RG serves on scientific advisory boards for Teva, Biogen, Bayer Schering Pharma, and Novartis; has received speaker honoraria from Biogen, Teva, Bayer Schering Pharma, and Novartis; serves as editor for Therapeutic Advances in Neurological Diseases and on the editorial boards of Experimental Neurology and the Journal of Neuroimmunology; receives research support from Teva, Biogen, Bayer Schering Pharma, Genzyme, Merck Serono, and Novartis; none related to this manuscript.