Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry.

Huemer, Martina; Diodato, Daria; Martinelli, Diego; Olivieri, Giorgia; Blom, Henk; Gleich, Florian; Kölker, Stefan; Kožich, Viktor; Morris, Andrew A; Seifert, Burkhardt; Froese, D Sean; Baumgartner, Matthias R; Dionisi-Vici, Carlo; Martin, Carlos Alcalde; Baethmann, Martina; Ballhausen, Diana; Blasco-Alonso, Javier; Boy, Nikolas; Bueno, Maria; Burgos Peláez, Rosa; ... (2019). Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: Data from the E-HOD registry. Journal of inherited metabolic diseases, 42(2), pp. 333-352. Wiley 10.1002/jimd.12041

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AIM To explore the clinical presentation, course, treatment and impact of early treatment in patients with remethylation disorders from the European Network and Registry for Homocystinurias and Methylation Defects (E-HOD) international web-based registry. RESULTS This review comprises 238 patients (cobalamin C defect n = 161; methylenetetrahydrofolate reductase deficiency n = 50; cobalamin G defect n = 11; cobalamin E defect n = 10; cobalamin D defect n = 5; and cobalamin J defect n = 1) from 47 centres for whom the E-HOD registry includes, as a minimum, data on medical history and enrolment visit. The duration of observation was 127 patient years. In 181 clinically diagnosed patients, the median age at presentation was 30 days (range 1 day to 42 years) and the median age at diagnosis was 3.7 months (range 3 days to 56 years). Seventy-five percent of pre-clinically diagnosed patients with cobalamin C disease became symptomatic within the first 15 days of life. Total homocysteine (tHcy), amino acids and urinary methylmalonic acid (MMA) were the most frequently assessed disease markers; confirmatory diagnostics were mainly molecular genetic studies. Remethylation disorders are multisystem diseases dominated by neurological and eye disease and failure to thrive. In this cohort, mortality, thromboembolic, psychiatric and renal disease were rarer than reported elsewhere. Early treatment correlates with lower overall morbidity but is less effective in preventing eye disease and cognitive impairment. The wide variation in treatment hampers the evaluation of particular therapeutic modalities. CONCLUSION Treatment improves the clinical course of remethylation disorders and reduces morbidity, especially if started early, but neurocognitive and eye symptoms are less responsive. Current treatment is highly variable. This study has the inevitable limitations of a retrospective, registry-based design.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Haematology, Oncology, Infectious Diseases, Laboratory Medicine and Hospital Pharmacy (DOLS) > Institute of Clinical Chemistry
04 Faculty of Medicine > Department of Gynaecology, Paediatrics and Endocrinology (DFKE) > Clinic of Paediatric Medicine

UniBE Contributor:

Gautschi, Matthias

Subjects:

600 Technology > 610 Medicine & health

ISSN:

0141-8955

Publisher:

Wiley

Language:

English

Submitter:

Alexandra Müller

Date Deposited:

03 Jan 2020 13:05

Last Modified:

06 Jan 2020 13:30

Publisher DOI:

10.1002/jimd.12041

PubMed ID:

30773687

BORIS DOI:

10.7892/boris.136912

URI:

https://boris.unibe.ch/id/eprint/136912

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