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

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@article{f907f55c3cc3442182aeda9a5e2021e7,
title = "Phenotype, treatment practice and outcome in the cobalamin-dependent remethylation disorders and MTHFR deficiency: data from the E-HOD registry",
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 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.",
author = "Martina Huemer and Daria Diodato and Diego Martinelli and Giorgia Olivieri and Henk Blom and Florian Gleich and Stefan K{\"o}lker and Viktor Ko{\v z}ich and Morris, {Andrew A} and Burkhardt Seifert and Froese, {D Sean} and Baumgartner, {Matthias R} and Carlo Dionisi-Vici and {Alcalde Martin}, C and M Baethmann and D Ballhausen and J Blasco-Alonso and N Boy and M Bueno and {Burgos Pel{\'a}ez}, R and R Cerone and B Chabrol and Chapman, {K A} and Couce, {M L} and E Crushell and {Dalmau Serra}, J and L Diogo and C Ficicioglu and {Garc{\'i}a Jimenez}, {M C} and {Garc{\'i}a Silva}, {M T} and Gaspar, {A M} and M Gautschi and D Gonz{\'a}lez-Lamu{\~n}o and S Gouveia and S Gr{\"u}newald and C Hendriksz and Janssen, {M C H} and P Jesina and J Koch and V Konstantopoulou and C Lavigne and Lund, {A M} and Martins, {E G} and {Meavilla Olivas}, S and K Mention and F Mochel and H Mundy and E Murphy and S Paquay and C Pedr{\'o}n-Giner and {EHOD consortium}",
year = "2019",
month = mar,
day = "12",
doi = "10.1007/s10545-018-0238-4",
language = "English",
journal = "Journal of Inherited Metabolic Disease",
issn = "0141-8955",
publisher = "Springer Netherlands",

}

RIS

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 - 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 - Alcalde Martin, C

AU - Baethmann, M

AU - Ballhausen, D

AU - Blasco-Alonso, J

AU - Boy, N

AU - Bueno, M

AU - Burgos Peláez, R

AU - Cerone, R

AU - Chabrol, B

AU - Chapman, K A

AU - Couce, M L

AU - Crushell, E

AU - Dalmau Serra, J

AU - Diogo, L

AU - Ficicioglu, C

AU - García Jimenez, M C

AU - García Silva, M T

AU - Gaspar, A M

AU - Gautschi, M

AU - González-Lamuño, D

AU - Gouveia, S

AU - Grünewald, S

AU - Hendriksz, C

AU - Janssen, M C H

AU - Jesina, P

AU - Koch, J

AU - Konstantopoulou, V

AU - Lavigne, C

AU - Lund, A M

AU - Martins, E G

AU - Meavilla Olivas, S

AU - Mention, K

AU - Mochel, F

AU - Mundy, H

AU - Murphy, E

AU - Paquay, S

AU - Pedrón-Giner, C

AU - EHOD consortium

PY - 2019/3/12

Y1 - 2019/3/12

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 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 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.

UR - http://www.scopus.com/inward/record.url?scp=85053387631&partnerID=8YFLogxK

U2 - 10.1007/s10545-018-0238-4

DO - 10.1007/s10545-018-0238-4

M3 - Journal article

C2 - 30178268

JO - Journal of Inherited Metabolic Disease

JF - Journal of Inherited Metabolic Disease

SN - 0141-8955

ER -

ID: 56312857