Header

UZH-Logo

Maintenance Infos

Manifestations of neurological symptoms and thromboembolism in adults with MTHFR-deficiency


Rommer, Paulus S; Zschocke, Johannes; Fowler, Brian; Födinger, Manuela; Konstantopoulou, Vassiliki; Möslinger, Dorothea; Stögmann, Elisabeth; Suess, Erhard; Baumgartner, Matthias; Auff, Eduard; Sunder-Plassmann, Gere (2017). Manifestations of neurological symptoms and thromboembolism in adults with MTHFR-deficiency. Journal of the Neurological Sciences, 383:123-127.

Abstract

BACKGROUND: Methylenetetrahydrofolate-reductase (MTHFR) deficiency is a rare autosomal recessive disorder affecting intracellular folate metabolism with affection of different organ systems and clinical manifestation usually in childhood.
OBJECTIVE: We report on four adult members of a family with MTHFR deficiency presenting with neurological and thromboembolic complications in adulthood.
METHODS: Extensive diagnostic work-up including genetic testing was performed in four adult members.
RESULTS: The male siblings aged 42 and 32years presented with various neurological symptoms, and a recent history of deep vein thrombosis. Extensive diagnostic work-up revealed total homocysteine (tHcy) plasma concentrations of 135μmol/L and 231μmol/L. and compound heterozygosity for two novel MTHFR gene mutations in exon 2 (c.202C>G, p.Arg68Gly) and intron 10 (c.1632+2T>G), and the known polymorphic variant MTHFR c.665C>T (p.Ala222Val, MTHFR 677C>T). Their mother was heterozygous for MTHFR c.1632+2T>G and c.665C>T, and a paternal relative was heterozygous for MTHFR c.202.C>G and MTHFR c.665C>T mutation. Both brothers showed partial response to therapy with betaine and multivitamins with clinical improvement. MTHFR activity was determined in fibroblast extracts and was around 4% of the mean control. Cell culture analysis indicated a re-methylation defect due to MTHFR deficiency.
CONCLUSION: Severe hyperhomocysteinemia due to two mutations of the MTHFR gene resulted in severe neurological symptoms in adulthood. Vitamin and methionine supplementation stabilize tHcy plasma levels. Severity of clinical manifestation varied greatly between the siblings. Damages to the nervous system may be present for years before becoming clinically manifest.

Abstract

BACKGROUND: Methylenetetrahydrofolate-reductase (MTHFR) deficiency is a rare autosomal recessive disorder affecting intracellular folate metabolism with affection of different organ systems and clinical manifestation usually in childhood.
OBJECTIVE: We report on four adult members of a family with MTHFR deficiency presenting with neurological and thromboembolic complications in adulthood.
METHODS: Extensive diagnostic work-up including genetic testing was performed in four adult members.
RESULTS: The male siblings aged 42 and 32years presented with various neurological symptoms, and a recent history of deep vein thrombosis. Extensive diagnostic work-up revealed total homocysteine (tHcy) plasma concentrations of 135μmol/L and 231μmol/L. and compound heterozygosity for two novel MTHFR gene mutations in exon 2 (c.202C>G, p.Arg68Gly) and intron 10 (c.1632+2T>G), and the known polymorphic variant MTHFR c.665C>T (p.Ala222Val, MTHFR 677C>T). Their mother was heterozygous for MTHFR c.1632+2T>G and c.665C>T, and a paternal relative was heterozygous for MTHFR c.202.C>G and MTHFR c.665C>T mutation. Both brothers showed partial response to therapy with betaine and multivitamins with clinical improvement. MTHFR activity was determined in fibroblast extracts and was around 4% of the mean control. Cell culture analysis indicated a re-methylation defect due to MTHFR deficiency.
CONCLUSION: Severe hyperhomocysteinemia due to two mutations of the MTHFR gene resulted in severe neurological symptoms in adulthood. Vitamin and methionine supplementation stabilize tHcy plasma levels. Severity of clinical manifestation varied greatly between the siblings. Damages to the nervous system may be present for years before becoming clinically manifest.

Statistics

Citations

Altmetrics

Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Children's Hospital Zurich > Medical Clinic
Dewey Decimal Classification:610 Medicine & health
Uncontrolled Keywords:Neurology, Clinical Neurology
Language:English
Date:15 December 2017
Deposited On:14 Feb 2018 14:27
Last Modified:19 Aug 2018 13:50
Publisher:Elsevier
ISSN:0022-510X
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/j.jns.2017.10.035
PubMed ID:29246599

Download

Full text not available from this repository.
View at publisher

Get full-text in a library