Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 333-352 |
| Number of pages | 20 |
| Journal | Journal of Inherited Metabolic Disease |
| Volume | 42 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2019 |
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Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency : Data from the E-HOD registry. / EHOD consortium.
In: Journal of Inherited Metabolic Disease, Vol. 42, No. 2, 03.2019, p. 333-352.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency
T2 - Data from the E-HOD registry
AU - EHOD consortium
AU - Huemer, Martina
AU - Diodato, Daria
AU - Martinelli, Diego
AU - Olivieri, Giorgia
AU - Blom, Henk
AU - Gleich, Florian
AU - Kölker, Stefan
AU - Kožich, Viktor
AU - Morris, Andrew A
AU - Seifert, Burkhardt
AU - Froese, D Sean
AU - Baumgartner, Matthias R
AU - Dionisi-Vici, Carlo
AU - Martin, Carlos Alcalde
AU - Baethmann, Martina
AU - Ballhausen, Diana
AU - Blasco-Alonso, Javier
AU - Boy, Nikolas
AU - Bueno, Maria
AU - Burgos Peláez, Rosa
AU - Cerone, Roberto
AU - Chabrol, Brigitte
AU - Chapman, Kimberly A
AU - Couce, Maria Luz
AU - Crushell, Ellen
AU - Dalmau Serra, Jaime
AU - Diogo, Luisa
AU - Ficicioglu, Can
AU - García Jimenez, Maria Concepcion
AU - García Silva, Maria Teresa
AU - Gaspar, Ana Maria
AU - Gautschi, Matthias
AU - González-Lamuño, Domingo
AU - Gouveia, Sofia
AU - Grünewald, Stephanie
AU - Hendriksz, Chris
AU - Janssen, Mirian C H
AU - Jesina, Pavel
AU - Koch, Johannes
AU - Konstantopoulou, Vassiliki
AU - Lavigne, Christian
AU - Lund, Allan M
AU - Martins, Esmeralda G
AU - Meavilla Olivas, Silvia
AU - Mention, Karine
AU - Mochel, Fanny
AU - Mundy, Helen
AU - Murphy, Elaine
AU - Paquay, Stephanie
AU - Pedrón-Giner, Consuelo
N1 - © 2018 SSIEM.
PY - 2019/3
Y1 - 2019/3
N2 - 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.
AB - 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.
U2 - 10.1002/jimd.12041
DO - 10.1002/jimd.12041
M3 - Article
C2 - 30773687
VL - 42
SP - 333
EP - 352
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
SN - 0141-8955
IS - 2
ER -