Abstract
Autosomal recessive disorders affecting pyridoxine (vitamin B6) metabolism are a rare but well-recognized cause of neonatal seizures. Antiquitin deficiency, caused by mutations in ALDH7A1, is a disorder of the lysine degradation pathway causing accumulation of an intermediate that complexes with pyridoxal phosphate. Reports of long-term follow-up of neonatal pyridoxine-dependent seizures (PDS) remain scarce and prognostic information is varied. We report a case of PDS in a 47-year-old lady who originally presented shortly after birth in 1964. Pyridoxine replacement was successful and diagnostic confirmation was obtained later in life, initially by biochemical analysis of serum pipecolic acid. Subsequently we organized genetic analysis of ALDH7A1, which revealed compound heterozygous mutations. To our knowledge, this represents the longest duration of follow-up published to date.
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Competing interests: None declared
Authors Markus Niemann and Arndt Rolfs contributed equally
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Mutation numbering has been updated to reflect the mitochondrial leader sequence. The missense mutation p.E427Q (RefSeq NM_001182.3) is the same mutation previously reported as E399Q (NM_001182.2) and the cryptic splicing mutation c.834G>A (NM_001182.3) was previously reported as c.750G>A (NM_001182.2). We initially failed to identify this as pathogenic in part due to this nomenclature change and also since only one of the four splicing prediction tools within Alamut ( www.interactive-biosoftware.com ) predicted an effect.
Communicated by: Cornelis Jakobs
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This report demonstrates an instance of long-term successful treatment of pyridoxine-dependent seizures, which was achieved without serious adverse effects.
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Proudfoot, M. et al. (2012). Long-Term Follow-up of a Successfully Treated Case of Congenital Pyridoxine-Dependent Epilepsy. In: Zschocke, J., Gibson, K., Brown, G., Morava, E., Peters, V. (eds) JIMD Reports - Volume 10. JIMD Reports, vol 10. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2012_210
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DOI: https://doi.org/10.1007/8904_2012_210
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