Clinical spectrum and genetic landscape of MTHFR deficiency: a cohort study including novel variants

Karalar Pekuz, ÖZGE; TEKE KISA, PELİN; Yildiz, Sevil; KOCABEY, MEHMET; ZÜBARİOĞLU, TANYEL; Arslan Gulten, ZÜMRÜT; Sezen, Emine; ER, Esra; Pekuz, Serdar; Kadioglu Yilmaz, Banu; Kirmizitas, MELİS; Ister, Meral; Kulu, BAHAR; Hazan, Filiz; KILIÇ, Mustafa; ÜNAL UZUN, ÖZLEM; KIYKIM, ERTUĞRUL; Aydin, Halil; ERDÖL, ŞAHİN; Aktuglu Zeybek, Ayse; ARSLAN, NUR

doi:10.1007/s10072-026-09447-w

Clinical spectrum and genetic landscape of MTHFR deficiency: a cohort study including novel variants

Karalar Pekuz O. K., TEKE KISA P., Yildiz S., KOCABEY M., ZÜBARİOĞLU T., Arslan Gulten Z., ...Daha Fazla

Neurological Sciences, cilt.47, sa.10, 2026 (SCI-Expanded, Scopus)

Yayın Türü: Makale / Tam Makale
Cilt numarası: 47 Sayı: 10
Basım Tarihi: 2026
Doi Numarası: 10.1007/s10072-026-09447-w
Dergi Adı: Neurological Sciences
Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, CINAHL, EMBASE, Index Islamicus, MEDLINE, Psycinfo, Academic Search Ultimate (EBSCO), Biomedical Reference Collection: Corporate Edition (EBSCO), Health Research Premium Collection (ProQuest), Pharma Collection (ProQuest), Psychology & Behavioral Sciences Collection (EBSCO)
Anahtar Kelimeler: Developmental delay, Epilepsy, Folate, Homocysteine, Methylene tetrahydrofolate reductase deficiency, MTHFR, MTHFR deficiency
Dokuz Eylül Üniversitesi Adresli: Evet

Özet

Methylene tetrahydrofolate reductase (MTHFR) deficiency is a rare inherited metabolic disorder that impairs myelination and brain development, leading to primary clinical manifestations, particularly neurological deficits. The aim of this study was to comprehensively describe the clinical presentation, biochemical profile, and molecular spectrum of patients with MTHFR deficiency. This multicenter, retrospective, descriptive study evaluated the medical records of 19 patients diagnosed with MTHFR deficiency at ten metabolic disease centers. A total of 13 patients had early-onset disease. In the early-onset group, all patients had varying degrees of neurodevelopmental delay. The median diagnostic delay from the first symptom to diagnosis was 3 months in early-onset cases and 118 months in late-onset cases. MTHFR deficiency exhibits a broad clinical spectrum, with acute deterioration possible even in chronically affected patients. MTHFR deficiency should be considered among treatable neurometabolic disorders in patients with otherwise unexplained neurodevelopmental or neuropsychiatric manifestations, particularly when accompanied by additional neurological findings.