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Metabolic Brain Disease

, Volume 34, Issue 5, pp 1515–1518 | Cite as

Novel mutations in two unrelated Italian patients with SSADH deficiency

  • Marta Balzarini
  • Valentina Rovelli
  • Sabrina Paci
  • Miriam Rigoldi
  • Giuseppina Sanna
  • Sara Pillai
  • Marilisa Asunis
  • Rossella Parini
  • Bianca Maria Ciminelli
  • Patrizia MalaspinaEmail author
Short Communication
  • 46 Downloads

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.

Keywords

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

Notes

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.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interests.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Marta Balzarini
    • 1
  • Valentina Rovelli
    • 2
  • Sabrina Paci
    • 2
  • Miriam Rigoldi
    • 3
  • Giuseppina Sanna
    • 4
  • Sara Pillai
    • 4
  • Marilisa Asunis
    • 5
  • Rossella Parini
    • 3
    • 6
  • Bianca Maria Ciminelli
    • 7
  • Patrizia Malaspina
    • 7
    Email author
  1. 1.Pediatric Clinic and Rare Disease DepartmentAntonio Cao Pediatric HospitalCagliariItaly
  2. 2.Pediatric Department, San Paolo Hospital, ASST Santi Paolo e CarloUniversity of MilanMilanItaly
  3. 3.Rare Metabolic Disease UnitSan Gerardo University HospitalMonzaItaly
  4. 4.Neonatal Screening CenterAntonio Cao Pediatric HospitalCagliariItaly
  5. 5.Pediatric Neurology DepartmentAntonio Cao Pediatric HospitalCagliariItaly
  6. 6.TIGET InstituteIRCCS San Raffaele HospitalMilanItaly
  7. 7.Department of BiologyUniversity of Rome Tor VergataRomeItaly

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