Abstract
Hereditary folate malabsorption is a rare autosomal recessive disorder caused by impaired active folate transport across membranes and into the central nervous system due to loss-of-function mutations in proton-coupled folate transporter (PCFT). Newborns with this condition have initially normal folate stores, but as they are unable to absorb dietary folate and use rapidly their stores because of their growth demands, symptoms appear in the early infancy. Significant neurological morbidity usually follows the initial non-specific clinical presentation and delayed initiation of treatment. High dose oral and parenteral folinic acid treatment have been previously reported in literature to improve the clinical outcome without achieving optimal cerebrospinal fluid (CSF) folate levels though. The active isomer of 5-formyltetrahydrofolate, also known as levofolinic acid, is available for administration. We report our experience in achieving normal (age dependent) CSF 5-Methyltetrahydrofolate (5-MTHF) levels following daily intramuscular administration of levofolinic acid in three patients with HFM. Follow-up assessment with repeated lumbar punctures has shown a stabilization of 5-MTHF levels within normal range. Clinical features and brain MRI findings had as well either improvement or stabilization. To the best of our knowledge, we provide as well for the first time data in regard to the im levofolinate treatment dosage.
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Communicated by: William Ross Wilcox, MD, PhD
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Take Home Message
Intramuscular levofolinate administration represents an alternative treatment option in HFM which seems to result in normal CSF 5-MTHF levels and improvement of clinical features.
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EM has written part of the paper.
PG has supervised and provided corrections for the paper.
SP has done the laboratory analysis and provided comments for the paper.
SJH has done the laboratory analysis and provided comments for the paper.
SB has supervised and written part of the paper.
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Spyros Batzios, Consultant in Paediatric Metabolic Medicine.
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Emanuela Manea, Paul Gissen, Simon Pope, Simon J. Heales, and Spyros Batzios declare that they have no conflict of interest.
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No experimental procedures were done in the human subjects which are reported in this paper so no ethical approval was required. All tests were done as part of the normal review of the patients. Parents gave informed consent for the publication of the paper.
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No animal is involved in this study.
This article does not contain any studies with human or animal subjects performed by the any of the authors.
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Manea, E., Gissen, P., Pope, S., Heales, S.J., Batzios, S. (2017). Role of Intramuscular Levofolinate Administration in the Treatment of Hereditary Folate Malabsorption: Report of Three Cases. In: Morava, E., Baumgartner, M., Patterson, M., Rahman, S., Zschocke, J., Peters, V. (eds) JIMD Reports, Volume 39. JIMD Reports, vol 39. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2017_39
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DOI: https://doi.org/10.1007/8904_2017_39
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