Incidence and Geographic Distribution of Succinic Semialdehyde Dehydrogenase (SSADH) Deficiency

  • Savita Verma Attri
  • Pratibha Singhi
  • Natrujee Wiwattanadittakul
  • Jyotindra N. Goswami
  • Naveen Sankhyan
  • Gajja S. Salomons
  • Jean-Baptiste Roullett
  • Ryan Hodgeman
  • Mahsa Parviz
  • K. Michael Gibson
  • Phillip L. Pearl
Research Report
Part of the JIMD Reports book series (JIMD, volume 34)

Abstract

The incidence of succinic semialdehyde dehydrogenase (SSADH) deficiency, an autosomal recessive inherited disorder of GABA degradation, is unknown. Upon a recent diagnosis of a new family of affected fraternal twins from the Punjabi ethnic group of India, case ascertainment from the literature and our database was done to determine the number of confirmed cases along with their geographic distribution. The probands presented with global developmental delay, infantile onset epilepsy, and a persistent neurodevelopmental disorder upon diagnosis at 10 years of age with intellectual disability, expressive aphasia, and behavioral problems most prominent for hyperactivity. Gamma-hydroxybutyric aciduria and homozygous ALDH5A1 c.608C>T; p.Pro203Leu mutations were confirmed. Identification of all available individual cases with clinical details available including geographic or ethnic origin revealed 182 patients from 40 countries, with the largest number of patients reported from the USA (24%), Turkey (10%), China (7%), Saudi Arabia (6%), and Germany (5%). This study provides an accounting of all published cases of confirmed SSADH deficiency and provides data useful in planning further studies of this rare inborn error of metabolism.

References

  1. Akaboshi S, Hogema BM, Novelletto A et al (2003) Mutational spectrum of the succinate semialdehyde dehydrogenase (ALDH5A1) gene and functional analysis of 27 novel disease-causing mutations in patients with SSADH deficiency. Hum Mutat 22:442–450CrossRefPubMedGoogle Scholar
  2. Aoshima T, Kajita M, Sekido Y et al (2002) Mutation analysis in a patient with succinic semialdehyde dehydrogenase deficiency: a compound heterozygote with 103-121del and 1460T > A of the ALDH5A1 gene. Hum Hered 53:42–44CrossRefPubMedGoogle Scholar
  3. Bekri S, Fossoud C, Plaza G et al (2004) The molecular basis of succinic semialdehyde dehydrogenase deficiency in one family. Mol Genet Metab 81:347–351CrossRefPubMedGoogle Scholar
  4. Brown GK, Cromby CH, Manning NJ, Pollitt RJ (1987) Urinary organic acids in succinic semialdehyde dehydrogenase deficiency: evidence of alpha-oxidation of 4-hydroxybutyric acid, interaction of succinic semialdehyde with pyruvate dehydrogenase and possible secondary inhibition of mitochondrial beta-oxidation. J Inherit Metab Dis 10:367–375CrossRefPubMedGoogle Scholar
  5. Dayan C, Ülker M, Akgün YH, Günaydin S, Atay T, Arpaci B (2006) Succinic semialdehyde dehydrogenase deficiency: three sibling in a family (case report). J Neurol Sci (Turkish) 23:129–134Google Scholar
  6. Deng XL, Yin F, Xiang QL, Liu CT, Peng J (2011) Succinic semialdehyde dehydrogenase deficiency. Zhongguo Dang Dai Er Ke Za Zhi 13:740–742PubMedGoogle Scholar
  7. Divry P, Baltassat P, Rolland MO et al (1983) A new patient with 4-hydroxybutyric aciduria, a possible defect of 4-aminobutyrate metabolism. Clin Chim Acta 129:303–309CrossRefPubMedGoogle Scholar
  8. Escalera GI, Ferrer I, Marina LC et al (2010) Succinic semialdehyde dehydrogenase deficiency: decrease in 4-OH-butyric acid levels with low doses of vigabatrin. An Pediatr (Barc) 72:128–132CrossRefGoogle Scholar
  9. Gibson KM, Christensen E, Jakobs C et al (1997) The clinical phenotype of succinic semialdehyde dehydrogenase deficiency (4-hydroxybutyric aciduria): case reports of 23 new patients. Pediatrics 99:567–574CrossRefPubMedGoogle Scholar
  10. Gibson KM, Gupta M, Pearl PL et al (2003) Significant behavioral disturbances in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria). Biol Psychiatry 54:763–768CrossRefPubMedGoogle Scholar
  11. Gogou M, Spilioti M, Tramma D, Papadopoulou-Alataki E, Evangeliou A (2016) Succinic semialdehyde dehydrogenase deficiency presenting as autism spectrum disorder. Indian J Pediatr 83:1036–1037CrossRefPubMedGoogle Scholar
  12. Haan EA, Brown GK, Mitchell D, Danks DM (1985) Succinic semialdehyde dehydrogenase deficiency--a further case. J Inherit Metab Dis 8:99CrossRefPubMedGoogle Scholar
  13. Ishiguro Y, Kajita M, Aoshima T, Watanabe K, Kimura M, Yamaguchi S (2001) The first case of 4-hydroxybutyric aciduria in Japan. Brain Dev 23:128–130CrossRefPubMedGoogle Scholar
  14. Jakobs C, Bojasch M, Monch E, Rating D, Siemes H, Hanefeld F (1981) Urinary excretion of gamma-hydroxybutyric acid in a patient with neurological abnormalities. The probability of a new inborn error of metabolism. Clin Chim Acta 111:169–178CrossRefPubMedGoogle Scholar
  15. Jiang SZ, Shu JB, Zhang YQ, Fan WX, Meng YT, Song L (2013) Analysis of ALDH5A1 gene mutation in a Chinese Han family with succinic semialdehyde dehydrogenase deficiency. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 30:389–393PubMedGoogle Scholar
  16. Kratz SV (2009) Sensory integration intervention: historical concepts, treatment strategies and clinical experiences in three patients with succinic semialdehyde dehydrogenase (SSADH) deficiency. J Inherit Metab Dis 32:353–360CrossRefPubMedGoogle Scholar
  17. Kwok JS, Yuen CL, Law LK, Tang NL, Cherk SW, Yuen YP (2012) A novel ALDH5A1 mutation in a patient with succinic semialdehyde dehydrogenase deficiency. Pathology 44:280–282CrossRefPubMedGoogle Scholar
  18. Lapalme-Remis S, Lewis EC, De Meulemeester C et al (2015) Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. Neurology 85:861–865CrossRefPubMedPubMedCentralGoogle Scholar
  19. Lemes A, Blasi P, Gonzales G et al (2006) Succinic semialdehyde dehydrogenase (SSADH) deficiency: molecular analysis in a South American family. J Inherit Metab Dis 29:587CrossRefPubMedGoogle Scholar
  20. Li X, Ding Y, Liu Y et al (2015) Succinic semialdehyde dehydrogenase deficiency of four Chinese patients and prenatal diagnosis for three fetuses. Gene 574:41–47CrossRefPubMedGoogle Scholar
  21. Lin CY, Weng WC, Lee WT (2015) A novel mutation of ALDH5A1 gene associated with succinic semialdehyde dehydrogenase deficiency. J Child Neurol 30:486–489CrossRefPubMedGoogle Scholar
  22. Liu N, Kong XD, Kan QC et al (2016) Mutation analysis and prenatal diagnosis in a Chinese family with succinic semialdehyde dehydrogenase and a systematic review of the literature of reported ALDH5A1 mutations. J Perinat Med 44:441–451CrossRefPubMedGoogle Scholar
  23. Neu P, Seyfert S, Brockmoller J, Dettling M, Marx P (2002) Neuroleptic malignant syndrome in a patient with succinic semialdehyde dehydrogenase deficiency. Pharmacopsychiatry 35:26–28CrossRefPubMedGoogle Scholar
  24. Niemi AK, Brown C, Moore T, Enns GM, Cowan TM (2014) Evidence of redox imbalance in a patient with succinic semialdehyde dehydrogenase deficiency. Mol Genet Metab Rep 1:129–132CrossRefPubMedPubMedCentralGoogle Scholar
  25. O’Rourke DJ, Ryan S, King MD (2010) Head bobbing due to succinic semialdehyde dehydrogenase deficiency. Neurology 74:2025CrossRefPubMedGoogle Scholar
  26. Onkenhout W, Maaswinkel-Mooij PD, Poorthuis BJ (1989) 4-Hydroxybutyric aciduria: further clinical heterogeneity in a new case. Eur J Pediatr 149:194–196CrossRefPubMedGoogle Scholar
  27. Parviz M, Vogel K, Gibson KM, Pearl PL (2014) Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 3:217–227CrossRefPubMedPubMedCentralGoogle Scholar
  28. Pearl PL, Novotny EJ, Acosta MT, Jakobs C, Gibson KM (2003) Succinic semialdehyde dehydrogenase deficiency in children and adults. Ann Neurol 54(Suppl 6):S73–S80CrossRefPubMedGoogle Scholar
  29. Pearl PL, Gibson KM, Cortez MA et al (2009) Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. J Inherit Metab Dis 32:343–352CrossRefPubMedPubMedCentralGoogle Scholar
  30. Peters H, Cleary M, Boneh A (1999) Succinic semialdehyde dehydrogenase deficiency in siblings: clinical heterogeneity and response to early treatment. J Inherit Metab Dis 22:198–199CrossRefPubMedGoogle Scholar
  31. Puttmann L, Stehr H, Garshasbi M et al (2013) A novel ALDH5A1 mutation is associated with succinic semialdehyde dehydrogenase deficiency and severe intellectual disability in an Iranian family. Am J Med Genet A 161A:1915–1922CrossRefPubMedGoogle Scholar
  32. Racaru VM, Pinard JM, Cheliout-Heraut F (2010) Sleep disorders in succinic semialdehyde dehydrogenase deficiency: a family report. Eur J Paediatr Neurol 14:282–287CrossRefPubMedGoogle Scholar
  33. Rashed M, Ozand PT, al Aqeel A, Gascon GG (1994) Experience of king faisal specialist hospital and research center with Saudi organic acid disorders. Brain Dev 16(Suppl):1–6CrossRefPubMedGoogle Scholar
  34. Rating D, Hanefeld F, Siemes H et al (1984) 4-Hydroxybutyric aciduria: a new inborn error of metabolism. I. Clinical review. J Inherit Metab Dis 7(Suppl 1):90–92CrossRefPubMedGoogle Scholar
  35. Saronwala A, Tournay A, Gargus JJ (2008) Taurine treatment of succinate semialdehyde dehydrogenase (SSADH) deficiency reverses MRI-documented globus lesion and clinical syndrome [abstract]. Proc Am Coll Med Genet 103Google Scholar
  36. Spilioti M, Evangeliou AE, Tramma D et al (2013) Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD). Front Hum Neurosci 7:858CrossRefPubMedPubMedCentralGoogle Scholar
  37. Tay CG, Ariffin H, Yap S, Rahmat K, Sthaneshwar P, Ong LC (2015) Succinic semialdehyde dehydrogenase deficiency in a Chinese boy: a novel ALDH5A1 mutation with severe phenotype. J Child Neurol 30:927–931CrossRefPubMedGoogle Scholar
  38. Wang KY, Barker PB, Lin DD (2016) A case of acute onset succinic semialdehyde dehydrogenase deficiency: neuroimaging findings and literature review. Child’s Nerv Syst 32:1305–1309Google Scholar
  39. Yamakawa Y, Nakazawa T, Ishida A et al (2012) A boy with a severe phenotype of succinic semialdehyde dehydrogenase deficiency. Brain Dev 34:107–112CrossRefPubMedGoogle Scholar
  40. Zhao XP, Liu GS, Song YZ (2003) A case of succinic semialdehyde dehydrogenase deficiency. Zhonghua Er Ke Za Zhi 41:719PubMedGoogle Scholar
  41. Ziyeh S, Berlis A, Korinthenberg R, Spreer J, Schumacher M (2002) Selective involvement of the globus pallidus and dentate nucleus in succinic semialdehyde dehydrogenase deficiency. Pediatr Radiol 32:598–600CrossRefPubMedGoogle Scholar

Copyright information

© Society for the Study of Inborn Errors of Metabolism (SSIEM) 2016

Authors and Affiliations

  • Savita Verma Attri
    • 1
  • Pratibha Singhi
    • 1
  • Natrujee Wiwattanadittakul
    • 2
  • Jyotindra N. Goswami
    • 1
  • Naveen Sankhyan
    • 1
  • Gajja S. Salomons
    • 3
  • Jean-Baptiste Roullett
    • 4
  • Ryan Hodgeman
    • 5
  • Mahsa Parviz
    • 5
  • K. Michael Gibson
    • 4
  • Phillip L. Pearl
    • 5
  1. 1.Department of PediatricsPGIMERChandigarhIndia
  2. 2.Department of PediatricsChiang Mai UniversityChiang MaiThailand
  3. 3.Department of Biological ChemistryVrje UniversityAmsterdamNetherlands
  4. 4.Experimental and Systems PharmacologyWashington State University, College of PharmacySpokaneUSA
  5. 5.Department of NeurologyBoston Children’s Hospital, Harvard Medical SchoolBostonUSA

Personalised recommendations