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Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis

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. CASE PRESENTATION: T...

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Autores principales: Motte, Jeremias, Fisse, Anna Lena, Grüter, Thomas, Schneider, Ruth, Breuer, Thomas, Lücke, Thomas, Krueger, Stefan, Nguyen, Huu Phuc, Gold, Ralf, Ayzenberg, Ilya, Ellrichmann, Gisa
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935479/
https://www.ncbi.nlm.nih.gov/pubmed/31884946
http://dx.doi.org/10.1186/s12883-019-1583-0
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author Motte, Jeremias
Fisse, Anna Lena
Grüter, Thomas
Schneider, Ruth
Breuer, Thomas
Lücke, Thomas
Krueger, Stefan
Nguyen, Huu Phuc
Gold, Ralf
Ayzenberg, Ilya
Ellrichmann, Gisa
author_facet Motte, Jeremias
Fisse, Anna Lena
Grüter, Thomas
Schneider, Ruth
Breuer, Thomas
Lücke, Thomas
Krueger, Stefan
Nguyen, Huu Phuc
Gold, Ralf
Ayzenberg, Ilya
Ellrichmann, Gisa
author_sort Motte, Jeremias
collection PubMed
description 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. 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 ALDH4A1 gene sequencing confirmed two previously unknown compound heterozygous variants (ALDH4A1 gene (NM_003748.3) Intron 1: c.62 + 1G > A - heterozygous and ALDH4A1 gene (NM_003748.3) Exon 5 c.349G > C, p.(Asp117His) - heterozygous). Under high-dose vitamin-B(6) therapy no further seizures occurred. CONCLUSION: We describe two novel 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.
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spelling pubmed-69354792019-12-30 Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis Motte, Jeremias Fisse, Anna Lena Grüter, Thomas Schneider, Ruth Breuer, Thomas Lücke, Thomas Krueger, Stefan Nguyen, Huu Phuc Gold, Ralf Ayzenberg, Ilya Ellrichmann, Gisa BMC Neurol Case Report 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. 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 ALDH4A1 gene sequencing confirmed two previously unknown compound heterozygous variants (ALDH4A1 gene (NM_003748.3) Intron 1: c.62 + 1G > A - heterozygous and ALDH4A1 gene (NM_003748.3) Exon 5 c.349G > C, p.(Asp117His) - heterozygous). Under high-dose vitamin-B(6) therapy no further seizures occurred. CONCLUSION: We describe two novel 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. BioMed Central 2019-12-29 /pmc/articles/PMC6935479/ /pubmed/31884946 http://dx.doi.org/10.1186/s12883-019-1583-0 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Case Report
Motte, Jeremias
Fisse, Anna Lena
Grüter, Thomas
Schneider, Ruth
Breuer, Thomas
Lücke, Thomas
Krueger, Stefan
Nguyen, Huu Phuc
Gold, Ralf
Ayzenberg, Ilya
Ellrichmann, Gisa
Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
title Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
title_full Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
title_fullStr Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
title_full_unstemmed Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
title_short Novel variants in a patient with late-onset hyperprolinemia type II: diagnostic key for status epilepticus and lactic acidosis
title_sort novel variants in a patient with late-onset hyperprolinemia type ii: diagnostic key for status epilepticus and lactic acidosis
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6935479/
https://www.ncbi.nlm.nih.gov/pubmed/31884946
http://dx.doi.org/10.1186/s12883-019-1583-0
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