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Novel mutations in two unrelated Italian patients with SSADH deficiency

Metabolic Brain Disease volume 34, pages 1515–1518 (2019)Cite this article

Abstract

Succinic semialdehyde dehydrogenase deficiency (SSADHD) is a rare autosomal recessive disorder of γ-aminobutyric acid (GABA) catabolism caused by mutations in the gene coding for succinic semialdehyde dehydrogenase (ALDH5A1). The abnormal levels of GHB detected in the brain and in all physiological fluids of SSADHD patients represent a diagnostic biochemical hallmark of the disease. Here we report on the clinical and molecular characterization of two unrelated Italian patients and the identification of two novel mutations: a 22 bp DNA duplication in exon 1, c.114_135dup, p.(C46AfsX97), and a non-sense mutation in exon 10, c.1429C > T, p.(Q477X). The two patients showed very different clinical phenotypes, coherent with their age. These findings enrich the characterization of SSADHD families and contribute to the knowledge on the progression of the disease.

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Acknowledgements

The authors would like to thank Cometa Sardegna Onlus Association for its support to the research. We also thank Dr. M. Lo Ponte for the English revision of the manuscript.

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Author notes

  1. Marta Balzarini and Valentina Rovelli contributed equally to the work.

Affiliations

  1. Pediatric Clinic and Rare Disease Department, Antonio Cao Pediatric Hospital, Cagliari, Italy

    Marta Balzarini

  2. Pediatric Department, San Paolo Hospital, ASST Santi Paolo e Carlo, University of Milan, Milan, Italy

    Valentina Rovelli & Sabrina Paci

  3. Rare Metabolic Disease Unit, San Gerardo University Hospital, Monza, Italy

    Miriam Rigoldi & Rossella Parini

  4. Neonatal Screening Center, Antonio Cao Pediatric Hospital, Cagliari, Italy

    Giuseppina Sanna & Sara Pillai

  5. Pediatric Neurology Department, Antonio Cao Pediatric Hospital, Cagliari, Italy

    Marilisa Asunis

  6. TIGET Institute, IRCCS San Raffaele Hospital, Milan, Italy

    Rossella Parini

  7. Department of Biology, University of Rome Tor Vergata, Via della Ricerca Scientifica, snc, 00133, Rome, Italy

    Bianca Maria Ciminelli & Patrizia Malaspina

Authors
  1. Marta Balzarini
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  2. Valentina Rovelli
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  3. Sabrina Paci
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  4. Miriam Rigoldi
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  5. Giuseppina Sanna
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  6. Sara Pillai
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  7. Marilisa Asunis
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  8. Rossella Parini
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  9. Bianca Maria Ciminelli
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  10. Patrizia Malaspina
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Correspondence to Patrizia Malaspina.

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Balzarini, M., Rovelli, V., Paci, S. et al. Novel mutations in two unrelated Italian patients with SSADH deficiency. Metab Brain Dis 34, 1515–1518 (2019). https://doi.org/10.1007/s11011-019-00453-w

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  • DOI: https://doi.org/10.1007/s11011-019-00453-w

Keywords

  • SSADHD (succinic semialdehyde dehydrogenase deficiency)
  • GABA (γ-aminobutyric acid)
  • GHB (γ-hydroxybutyric acid)
  • ALDH5A1 gene
  • 4-HBA (4-hydroxybutiric aciduria)