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A female case of 5,10-methenyltetrahydrofolate synthetase deficiency with novel neuro-imaging abnormalities

  • Author Footnotes
    1 ORCID ID: 0000-0003-4924-5300.
    Dilek Cavusoglu
    Correspondence
    Corresponding author at: Department of Pediatric Neurology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Ali Çetinkaya Kampüsü Dörtyol Mah. 2078 Sok. No. 3/4 Afyonkarahisar, Afyon 03100, Turkey.
    Footnotes
    1 ORCID ID: 0000-0003-4924-5300.
    Affiliations
    Department of Pediatric Neurology, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyon, Turkey
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  • Author Footnotes
    2 ORCID ID: 0000-0003-2255-3725.
    Melis Kose
    Footnotes
    2 ORCID ID: 0000-0003-2255-3725.
    Affiliations
    Department of Pediatric Metabolism and Nutrition, Faculty of Medicine, İzmir Katip Celebi University, Izmir, Turkey
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  • Author Footnotes
    3 ORCID ID: 0000-0001-8867-0508.
    Esra Er
    Footnotes
    3 ORCID ID: 0000-0001-8867-0508.
    Affiliations
    Department of Pediatric Metabolism and Nutrition, Health Sciences University, Tepecik Training and Research Hospital, Izmir, Turkey
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  • Author Footnotes
    4 ORCID ID: 0000-0002-5626-2160.
    Muhsin Elmas
    Footnotes
    4 ORCID ID: 0000-0002-5626-2160.
    Affiliations
    Department of Medical Genetics, Faculty of Medicine, Afyonkarahisar Health Sciences University, Afyon, Turkey
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  • Author Footnotes
    5 ORCID ID: 0000-0002-3223-5408.
    Pinar Gencpinar
    Footnotes
    5 ORCID ID: 0000-0002-3223-5408.
    Affiliations
    Department of Pediatric Neurology, Faculty of Medicine, İzmir Katip Celebi University, Izmir, Turkey
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  • Author Footnotes
    6 ORCID ID: 0000-0002-5902-3501.
    Nihal Olgaç Dundar
    Footnotes
    6 ORCID ID: 0000-0002-5902-3501.
    Affiliations
    Department of Pediatric Neurology, Faculty of Medicine, İzmir Katip Celebi University, Izmir, Turkey
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  • Author Footnotes
    7 ORCID ID: 0000-0003-1513-6149.
    Kursad Aydin
    Footnotes
    7 ORCID ID: 0000-0003-1513-6149.
    Affiliations
    Department of Pediatric Neurology, Istanbul Medipol University, Istanbul, Turkey
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  • Author Footnotes
    1 ORCID ID: 0000-0003-4924-5300.
    2 ORCID ID: 0000-0003-2255-3725.
    3 ORCID ID: 0000-0001-8867-0508.
    4 ORCID ID: 0000-0002-5626-2160.
    5 ORCID ID: 0000-0002-3223-5408.
    6 ORCID ID: 0000-0002-5902-3501.
    7 ORCID ID: 0000-0003-1513-6149.

      Abstract

      Background

      Folate metabolism disorders can affect various organ systems, including the nervous system. 5,10-methenyltetrahydrofolate synthetase deficiency is a rare cerebral folate deficiency in which MTHFS activity is disrupted with low-normal cerebrospinal fluid (CSF) 5,10-methenyltetrahydrofolate levels, while peripheral folate levels are normal.

      Case report

      We present here a female patient with developmental delay, microcephaly, hypotonia, nystagmus, and seizure in which a distinct brain MRI and CT showed restricted diffusion in the bilateral parietal and occipital lobes, and calcifications of the bilateral putamen, globus pallidus, and caudate nucleus, and the bilateral parietal and occipital lobes. Laboratory tests revealed macrocytic anemia, increased homocysteine, low-normal CSF 5,10-methenyltetrahydrofolate, and low CSF folate, but normal serum vitamin B12 and folate levels. A whole exome sequencing analysis verified the diagnosis of 5,10-methenyltetrahydrofolate synthetase deficiency.

      Conclusions

      We have added novel knowledge which is nystagmus and hypotonia in the clinical findings, the involvement and restriction of bilateral putamen, globus pallidus, parietal and occipital lobes, and calcification of the bilateral putamen, globus pallidus, caudate nucleus, and parietal and occipital lobes in neuroimaging images and also low CSF folate in the metabolic investigation with the patient in 5,10-methenyltetrahydrofolate synthetase deficiency.

      Keywords

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