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Jeremias Motte, Anna Lena Fisse, Thomas Grüter, Ruth Schneider, Thomas Georg Karl Breuer, Thomas Lücke, Stefan Krüger, Huu Phuc Nguyen, Ralf Gold, Ilya Ayzenberg, Gisa Ellrichmann

• \(\bf Background\) Hyperprolinemia type 2 (HPII) is a rare autosomal recessive disorder of the proline metabolism, that affects the ALDH4A1 gene. So far only four different pathogenic mutations are known. The manifestation is mostly in neonatal age, in early infancy or early childhood. \(\bf Case presentation\) The 64-years female patient had a long history of abdominal pain, and episode of an acute neuritis. Ten years later she was admitted into the neurological intensive-care-unit with acute abdominal pain, multiple generalized epileptic seizures, a vertical gaze palsy accompanied by extensive lactic acidosis in serum 26.0 mmol/l (reference: 0.55–2.2 mmol/l) and CSF 12.01 mmol/l (reference: 1.12–2.47 mmol/l). Due to repeated epileptic seizures and secondary complications a long-term sedation with a ventilation therapy over 20 days was administered. A diagnostic work-up revealed up to 400-times increased prolin-level in urine CSF and blood. Furthermore, a low vitamin-B\(_6\) serum value was found, consistent with a HPII causing secondary pyridoxine deficiency and seizures. The \(\it ALDH4A1\) gene sequencing confirmed two previously unknown compound heterozygous variants (\(\it ALDH4A1\) gene (NM_003748.3) Intron 1: c.62 + 1G > A - heterozygous and \(\it ALDH4A1\) gene (NM_003748.3) Exon 5 c.349G > C, p.(Asp117His) - heterozygous). Under high-dose vitamin-B\(_6\) therapy no further seizures occurred. \(\bf Conclusion\) We describe two novel \(\it ALDH4A1\)-variants in an adult patient with hyperprolinemia type II causing secondary pyridoxine deficiency and seizures. Severe and potentially life-threatening course of this treatable disease emphasizes the importance of diagnostic vigilance and thorough laboratory work-up including gene analysis even in cases with atypical late manifestation.