Skip to main content
SpringerLink
Log in

Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism

  • Review
  • Published:
Journal of Inherited Metabolic Disease

Abstract

This review summarizes a presentation made at the retirement Symposium of Prof. Dr. Cornelis Jakobs in November of 2011, highlighting the progress toward clinical trials in succinic semialdehyde dehydrogenase (SSADH) deficiency, a disorder first recognized in 1981. Active and potential clinical interventions, including vigabatrin, L-cycloserine, the GHB receptor antagonist NCS-382, and the ketogenic diet, are discussed. Several biomarkers to gauge clinical efficacy have been identified, including cerebrospinal fluid metabolites, neuropsychiatric testing, MRI, EEG, and measures of GABAergic function including (11 C)flumazenil positron emission tomography (PET) and transcranial magnetic stimulation (TMS). Thirty years after its discovery, encompassing extensive studies in both patients and the corresponding murine model, we are now running an open-label trial of taurine intervention, and are poised to undertake a phase II trial of the GABAB receptor antagonist SGS742.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Abbreviations

ABAS-II:

adaptive behavior assessment scale II

ACTH:

adrenocorticotropic hormone

ADHD:

attention deficit hyperactivity disorder

AED:

antiepileptic drug

BBB:

blood brain barrier

CSF:

cerebrospinal fluid

DA:

dopamine

EEG:

electroencephalography

FDA:

Food and Drug Administration (of the USA)

FMZ:

flumazenil (GABAAR ligand benzodiazepine binding site)

GABA:

4-aminobutyric acid

GABAAR:

GABAA receptor

GABABR:

GABAB receptor

GABA-T:

GABA-transaminase

GAD:

glutamic acid decarboxylase

GHB:

4-hydroxybutyric acid

GHBR:

GHB receptor

IND:

investigational new drug

IQ:

intelligence quotient

IS:

infantile spasms

KD:

ketogenic diet

LCS:

L-cycloserine

MCI:

mild cognitive impairment

MRI:

magnetic resonance imaging

NCS-382:

(6,7,8,9-tetrahydro-5-hydroxy-5 H-benzocyclohept-6-ylidene)acetic acid

SGS742:

phosphinic acid (3-aminopropyl)butyl-

SSADH:

succinic semialdehyde dehydrogenase (or ALDH5A1 aldehyde dehydrogenase 5a1)

TMS:

transcranial magnetic stimulation

TCA:

tricarboxylic acid

VGB:

vigabatrin (gamma-vinyl GABA; SabrilR (Lundbeck Corporation))

References

  • Aldini G, Facino RM, Beretta G, Carini M (2005) Carnosine and related dipeptides as quenchers of reactive carbonyl species: from structural studies to therapeutic perspectives. Biofactors 24:77–87

    Article  PubMed  CAS  Google Scholar 

  • Al-Essa MA, Bakheet SM, Patay ZJ, Powe JE, Ozand PT (2000) Clinical, fluorine-18 labeled 2-fluoro-2-deoxyglucose positron emission tomography (FDG PET), MRI of the brain and biochemical observations in a patient with 4-hydroxybutyric aciduria; a progressive neurometabolic disease. Brain Dev 22:127–131

    Article  PubMed  CAS  Google Scholar 

  • Bauer K (2005) Carnosine and homocarnosine, the forgotten, enigmatic peptides of the brain. Neurochem Res 30:1339–1345

    Article  PubMed  CAS  Google Scholar 

  • Beuster G, Zarse K, Kaleta C et al (2011) Inhibition of alanine aminotransferase in silico and in vivo promotes mitochondrial metabolism to impair malignant growth. J Biol Chem 286:22323–22330

    Article  PubMed  CAS  Google Scholar 

  • Bowery NG (2006) GABAB receptor: a site of therapeutic benefit. Curr Opin Pharmacol 6:37–43

    Article  PubMed  CAS  Google Scholar 

  • Bullock R (2005) SGS-742 Novartis. Curr Opin Investig Drugs 6:108–113

    PubMed  CAS  Google Scholar 

  • Butler WH, Ford GP, Newberne JW (1987) A study of the effects of vigabatrin on the central nervous system and retina of Sprague Dawley and Lister-hooded rats. Toxicol Pathol 15:143–148

    Article  PubMed  CAS  Google Scholar 

  • Buzzi A, Wu Y, Frantseva MV et al (2006) Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. Brain Res 1090:15–22

    Article  PubMed  CAS  Google Scholar 

  • Casarano M, Alessandri MG, Salomons GS et al (2011) Efficacy of vigabatrin intervention in a mild phenotypic expression of succinic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis (JIMD Reports) 2:119–123

    Google Scholar 

  • Chambliss KL, Zhang YA, Rossier E, Vollmer B, Gibson KM (1995) Enzymatic and immunologic identification of succinic semialdehyde dehydrogenase in rat and human neural and nonneural tissues. J Neurochem 65:851–855

    Article  PubMed  CAS  Google Scholar 

  • Cho JY (2007) Effect of L-cycloserine on cellular responses mediated by macrophages and T cells. Biol Pharm Bull 30:2105–2112

    Article  PubMed  CAS  Google Scholar 

  • Cortez MA, Wu Y, Gibson KM, Snead OC (2004) Absence seizures in succinic semialdehyde dehydrogenase deficient mice: a model of juvenile absence epilepsy. Pharmacol Biochem Behav 79:547–553

    Article  PubMed  CAS  Google Scholar 

  • Cusmai R, Martinelli D, Moavero R et al (2012) Ketogenic diet in early myoclonic encephalopathy due to non ketotic hyperglycinemia. Eur J Paediatr Neurol Jan 17 [Epub ahead of print]

  • Daune G, Seiler N (1988) Interrelationships between ornithine, glutamate, and GABA. II. Consequences of inhibition of GABA-T and ornithine aminotransferase in brain. Neurochem Res 13:69–75

    Article  PubMed  CAS  Google Scholar 

  • De Biase D, Simmaco M, Barra D, Bossa F, Hewlins M, John RA (1991) Mechanism of inactivation and identification of sites of modification of ornithine aminotransferase by 4-aminohex-5-ynoate. Biochemistry 30:2239–2246

    Article  PubMed  Google Scholar 

  • de Vries PM, de Jong BM, Bohning DE, Hinson VK, George MS, Leenders KL (2012) Reduced parietal activation in cervical dystonia after parietal TMS interleaved with fMRI. Clin Neurol Neurosurg Mar 1 [Epub ahead of print]

  • Ergezinger K, Jeschke R, Frauendienst-Egger G, Korall H, Gibson KM, Schuster VH (2003) Monitoring of 4-hydroxybutyric acid levels in body fluids during vigabatrin treatment in succinic semialdehyde dehydrogenase deficiency. Ann Neurol 54:686–689

    Article  PubMed  CAS  Google Scholar 

  • 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) 72:128–132

    Article  Google Scholar 

  • Farlow MR (2009) Treatment of mild cognitive impairment (MCI). Curr Alzheimer Res 6:362–367

    Article  PubMed  CAS  Google Scholar 

  • Froestl W, Gallagher M, Jenkins H et al (2004) SGS742: the first GABA(B) receptor antagonist in clinical trials. Biochem Pharmacol 68:1479–1487

    Article  PubMed  CAS  Google Scholar 

  • Gibson KM, Sweetman L, Nyhan WL et al (1983) Succinic semialdehyde dehydrogenase deficiency: an inborn error of gamma-aminobutyric acid metabolism. Clin Chim Acta 133:33–42

    Article  PubMed  CAS  Google Scholar 

  • Gibson KM, DeVivo DC, Jakobs C (1989) Vigabatrin therapy in patient with succinic semialdehyde dehydrogenase deficiency. Lancet 2:1105–1106

    Article  PubMed  CAS  Google Scholar 

  • Gibson KM, Jakobs C, Ogier H et al (1995) Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis 18:143–146

    Article  PubMed  CAS  Google Scholar 

  • 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 99:567–574

    Article  PubMed  CAS  Google Scholar 

  • Gibson KM, Schor DS, Gupta M et al (2002) Focal neurometabolic alterations in mice deficient for succinate semialdehyde dehydrogenase. J Neurochem 81:71–79

    Article  PubMed  CAS  Google Scholar 

  • Gropman A (2003) Vigabatrin and newer interventions in succinic semialdehyde dehydrogenase deficiency. Ann Neurol 54:S66–S72

    Article  PubMed  CAS  Google Scholar 

  • Gupta M, Greven R, Jansen EE et al (2002) Therapeutic intervention in mice deficient for succinate semialdehyde dehydrogenase (gamma-hydroxybutyric aciduria). J Pharmacol Exp Ther 302:180–187

    Article  PubMed  CAS  Google Scholar 

  • Gupta M, Polinsky M, Senephansiri H et al (2004a) Seizure evolution and amino acid imbalances in murine succinate semialdehyde dehydrogenase (SSADH) deficiency. Neurobiol Dis 16:556–562

    Article  PubMed  CAS  Google Scholar 

  • Gupta M, Jansen EE, Senephansiri H et al (2004b) Liver-directed adenoviral gene transfer in murine succinate semialdehyde dehydrogenase deficiency. Mol Ther 9:527–539

    Article  PubMed  CAS  Google Scholar 

  • Herlenius E, Lagercrantz H (2001) Neurotransmitters and neuromodulators during early human development. Early Hum Dev 65:21–37

    Article  PubMed  CAS  Google Scholar 

  • Hogema BM, Gupta M, Senephansiri H et al (2001) Pharmacologic rescue of lethal seizures in mice deficient in succinate semialdehyde dehydrogenase. Nat Genet 29:212–216

    Article  PubMed  CAS  Google Scholar 

  • Jaeken J, Casaer P, de Cock P et al (1984) Gamma-aminobutyric acid-transaminase deficiency: a newly recognized inborn error of neurotransmitter metabolism. Neuropediatrics 15:165–169

    Article  PubMed  CAS  Google Scholar 

  • Jaeken J, Casaer P, de Cock P, Francois B (1989) Vigabatrin in GABA metabolism disorders. Lancet 1:1074

    Article  PubMed  CAS  Google Scholar 

  • Jakobs C, Bojasch M, Mönch 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 111:169–178

    Article  PubMed  CAS  Google Scholar 

  • Jakobs C, Michael T, Jaeger E, Jaeken J, Gibson KM (1992) Further evaluation of vigabatrin therapy in 4-hydroxybutyric aciduria. Eur J Pediatr 151:466

    Article  PubMed  CAS  Google Scholar 

  • Jansen EE, Struys E, Jakobs C, Hager E, Snead OC, Gibson KM (2008) Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH) deficiency suggest a heightened excitatory state during development. BMC Dev Biol 8:112

    Article  PubMed  Google Scholar 

  • Knerr I, Pearl PL, Bottiglieri T, Snead OC, Jakobs C, Gibson KM (2007) Therapeutic concepts in succinate semialdehyde dehydrogenase (SSADH; ALDH5a1) deficiency (gamma-hydroxybutyric aciduria). Hypotheses evolved from 25 years of patient evaluation, studies in Aldh5a1-/- mice and characterization of gamma-hydroxybutyric acid pharmacology. J Inherit Metab Dis 30:279–294

    Article  PubMed  CAS  Google Scholar 

  • Krauss GL, Johnson MA, Miller NR (1998) Vigabatrin-associated retinal cone system dysfunction: electroretinogram and ophthalmologic findings. Neurology 50:614–618

    Article  PubMed  CAS  Google Scholar 

  • Louzada PR, Paula Lima AC, Mendonca-Silva DL, Noël F, De Mello FG, Ferreira ST (2004) Taurine prevents the neurotoxicity of beta-amyloid and glutamate receptor agonists: activation of GABA receptors and possible implications for Alzheimer's disease and other neurological disorders. FASEB J 18:511–518

    Article  PubMed  CAS  Google Scholar 

  • Lowther J, Yard BA, Johnson KA et al (2010) Inhibition of the PLP-dependent enzyme serine palmitoyltransferase by cycloserine: evidence for a novel decarboxylative mechanism of inactivation. Mol Biosyst 6:1682–1693

    Article  PubMed  CAS  Google Scholar 

  • Maitre M (1997) The gamma-hydroxybutyrate signalling system in brain: organization and functional implications. Prog Neurobiol 51:337–361

    Article  PubMed  CAS  Google Scholar 

  • Marescaux C, Micheletti G, Vergnes M, Rumbach L, Warter JM (1985) Diazepam antagonizes GABAmimetics in rats with spontaneous petit mal-like epilepsy. Eur J Pharmacol 113:19–24

    Article  PubMed  CAS  Google Scholar 

  • Matern D, Lehnert W, Gibson KM, Korinthenberg R (1996) Seizures in a boy with succinic semialdehyde dehydrogenase deficiency treated with vigabatrin (gamma-vinyl-GABA). J Inherit Metab Dis 19:313–318

    Article  PubMed  CAS  Google Scholar 

  • McNally MA, Hartman AL (2012) Ketone bodies in epilepsy. J Neurochem Jan 23 [Epub ahead of print]

  • Mehta AK, Gould GG, Gupta M, Carter LP, Gibson KM, Ticku MK (2006) Succinate semialdehyde dehydrogenase deficiency does not down-regulate gamma-hydroxybutyric acid binding sites in the mouse brain. Mol Genet Metab 88:86–89

    Article  PubMed  CAS  Google Scholar 

  • Murphy TC, Amarnath V, Gibson KM, Picklo MJ Sr (2003) Oxidation of 4-hydroxy-2-nonenal by succinic semialdehyde dehydrogenase (ALDH5A1). J Neurochem 86:298–305

    Article  PubMed  CAS  Google Scholar 

  • Netopilová M, Drsata J, Haugvicová R, Kubová H, Mares P (1997) Inhibition of glutamate decarboxylase activity by 3-mercaptopropionic acid has different time course in the immature and adult rat brains. Neurosci Lett 226:68–70

    Article  PubMed  Google Scholar 

  • Nylen K, Velazquez JL, Likhodii SS et al (2008) A ketogenic diet rescues the murine succinic semialdehyde dehydrogenase deficient phenotype. Exp Neurol 210:449–457

    Article  PubMed  CAS  Google Scholar 

  • Nylen K, Velazquez JL, Sayed V, Gibson KM, Burnham WM, Snead OC (2009) The effects of a ketogenic diet on ATP concentrations and the number of hippocampal mitochondria in Aldh5a1(-/-) mice. Biochim Biophys Acta 1790:208–212

    Article  PubMed  CAS  Google Scholar 

  • Oermann E, Warskulat U, Heller-Stilb B, Häussinger D, Zilles K (2005) Taurine-transporter gene knockout-induced changes in GABA(A), kainate and AMPA but not NMDA receptor binding in mouse brain. Anat Embryol (Berl) 210:363–372

    Article  CAS  Google Scholar 

  • Olive MF (2002) Interactions between taurine and ethanol in the central nervous system. Amino Acids 23:345–357

    Article  PubMed  CAS  Google Scholar 

  • Pearl PL, Gropman A (2004) Monitoring gamma-hydroxybutyric acid levels in succinate-semialdehyde dehydrogenase deficiency. Ann Neurol 55:599–599

    Article  PubMed  Google Scholar 

  • Pearl PL, Gibson KM, Acosta MT et al (2003) Clinical spectrum of succinic semialdehyde dehydrogenase deficiency. Neurology 60:1413–1417

    Google Scholar 

  • Pearl PL, Gibson KM, Quezado Z et al (2009a) Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. Neurology 73:423–429

    Article  PubMed  CAS  Google Scholar 

  • Pearl PL, Vezina LG, Saneto RP et al (2009b) Cerebral MRI abnormalities associated with vigabatrin therapy. Epilepsia 50:184–194

    Article  PubMed  CAS  Google Scholar 

  • Pearl PL, Gibson KM, Cortez MA et al (2009c) Succinic semialdehyde dehydrogenase deficiency: lessons from mice and men. J Inherit Metab Dis 32:343–352

    Article  PubMed  CAS  Google Scholar 

  • Pearl PL, Shukla L, Theodore WH, Jakobs C, Michael Gibson K (2011) Epilepsy in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. Brain Dev 33:796–805

    Article  PubMed  Google Scholar 

  • Pearl PL, Theodore WH, McCarter R, McGavin C, Sweetman L, Gibson KM (2012) Taurine intervention in succinic semialdehyde dehydrogenase (SSADH) deficiency: an open label trial. Molec Genet Metab 105:346, abstract

    Google Scholar 

  • Peyster RG, Sussman NM, Hershey BL et al (1995) Use of ex vivo magnetic resonance imaging to detect onset of vigabatrin-induced intramyelinic edema in canine brain. Epilepsia 36:93–100

    Article  PubMed  CAS  Google Scholar 

  • Polc P, Pieri L, Bonetti EP et al (1986) L-cycloserine: behavioural and biochemical effects after single and repeated administration to mice, rats and cats. Neuropharmacology 25:411–418

    Article  PubMed  CAS  Google Scholar 

  • Qiao M, Malisza KL, Del Bigio MR, Kozlowski P, Seshia SS, Tuor UI (2000) Effect of long-term vigabatrin administration on the immature rat brain. Epilepsia 41:655–665

    Article  PubMed  CAS  Google Scholar 

  • Rahbeeni Z, Ozand PT, Rashed M et al (1994) 4-Hydroxybutyric aciduria. Brain Dev 16(Suppl):64–71

    Article  PubMed  Google Scholar 

  • Reis J, Cohen LG, Pearl PL et al (2012) GABA(B)ergic motor dysfunction in SSADH deficiency. Neurology, in press

  • Rheims S, Minlebaev M, Ivanov A et al (2008) Excitatory GABA in rodent developing neocortex in vitro. J Neurophysiol 100:609–619

    Article  PubMed  Google Scholar 

  • Roberts F, Taberner PV, Hill RG (1978) The effect of 3-mercaptopropionate, an inhibitor of glutamate decarboxylase, on the levels of GABA and other amino acids, and on presynaptic inhibition in the rat cuneate nucleus. Neuropharmacology 17:715–720

    Article  PubMed  CAS  Google Scholar 

  • Saronwala A, Tournay A, Gargus JJ (2008) Taurine treatment of succinate semialdehyde dehydrogenase (SSADH) deficiency reverses MRI-documented globus lesion and clinical syndrome. Am Coll Med Genet, 15th Ann Clinical Genet Meeting, March 12-16, Phoenix AZ USA, p. 103

  • Snead OC (1978) Gamma hydroxybutyrate in the monkey. I. Electroencephalographic, behavioral, and pharmacokinetic studies. Neurology 28:636–642

    Article  PubMed  CAS  Google Scholar 

  • Snead OC (2000) Evidence for a G protein-coupled gamma-hydroxybutyric acid receptor. J Neurochem 75:1986–1996

    Article  PubMed  CAS  Google Scholar 

  • Snead OC, Gibson KM (2005) Gamma-hydroxybutyric acid. N Engl J Med 352:2721–2732

    Article  PubMed  CAS  Google Scholar 

  • Sorri I, Brigell MG, Mályusz M, Mahlamäki E, de Meynard C, Kälviäinen R (2010) Is reduced ornithine-δ-aminotransferase activity the cause of vigabatrin-associated visual field defects? Epilepsy Res 92:48–53

    Article  PubMed  CAS  Google Scholar 

  • Spence SJ, Sankar R (2001) Visual field defects and other ophthalmological disturbances associated with vigabatrin. Drug Saf 24:385–404

    Article  PubMed  CAS  Google Scholar 

  • Stewart LS, Nylen KJ, Persinger MA, Cortez MA, Gibson KM, Snead OC (2008) Circadian distribution of generalized tonic-clonic seizures associated with murine succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. Epilepsy Behav 13:290–294

    Article  PubMed  Google Scholar 

  • Tillakaratne NJ, Medina-Kauwe L, Gibson KM (1995) γ-Aminobutyric acid (GABA) metabolism in mammalian neural and nonneural tissues. Comp Biochem Physiol A Physiol 112:247–263

    Article  PubMed  CAS  Google Scholar 

  • Tomi M, Tajima A, Tachikawa M, Hosoya K (2008) Function of taurine transporter (Slc6a6/TauT) as a GABA transporting protein and its relevance to GABA transport in rat retinal capillary endothelial cells. Biochim Biophys Acta 1778:2138–2142

    Article  PubMed  CAS  Google Scholar 

  • Tsuji M, Aida N, Obata T et al (2010) A new case of GABA transaminase deficiency facilitated by proton MR spectroscopy. J Inherit Metab Dis 33:85–90

    Article  PubMed  CAS  Google Scholar 

  • Uziel G, Bardelli P, Pantaleoni C, Rimoldi M, Savoiardo M (1993) 4-Hydroxybutyric aciduria: clinical findings and vigabatrin therapy. J Inherit Metab Dis 16:520–522

    Article  PubMed  CAS  Google Scholar 

  • Vanadia E, Gibson KM, Pearl PL, Trapolino E, Mangano S, Vanadia F (2012) Therapeutic efficacy of magnesium valproate in succinic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis (in press)

  • Vanhatalo S, Nousiainen I, Eriksson K et al (2002) Visual field constriction in 91 Finnish children treated with vigabatrin. Epilepsia 43:748–756

    Article  PubMed  Google Scholar 

  • Waagepetersen HS, Sonnewald U, Schousboe A (1999) The GABA paradox: multiple roles as metabolite, neurotransmitter, and neurodifferentiative agent. J Neurochem 73:1335–1342

    Article  PubMed  CAS  Google Scholar 

  • Wong CG, Gibson KM, Snead OC (2004) From the street to the brain: neurobiology of the recreational drug gamma-hydroxybutyric acid. Trends Pharmacol Sci 25:29–34

    Article  PubMed  CAS  Google Scholar 

  • Wu Y, Buzzi A, Frantseva M et al (2006) Status epilepticus in mice deficient for succinate semialdehyde dehydrogenase: GABAA receptor-mediated mechanisms. Ann Neurol 59:42–52

    Article  PubMed  CAS  Google Scholar 

  • Yalçinkaya C, Gibson KM, Gündüz E, Koçer N, Fiçicioğlu C, Küçükercan I (2000) MRI findings in succinic semialdehyde dehydrogenase deficiency. Neuropediatrics 31:45–46

    Article  PubMed  Google Scholar 

  • 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 32:598–600

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge Dr. Boris M. Hogema, who developed the murine model. The funding and support of the NIH (HD 58553) and the Pediatric Neurotransmitter Disease Association are gratefully acknowledged. This research was also supported by awards UL1RR031988 and P30HD40677 from the NIH National Center for Research Resources and NIH Intellectual and Developmental Disabilities Research Center, respectively.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Section of Clinical Pharmacology, College of Pharmacy, Washington State University, SAC 520, 412 E. Spokane Falls Blvd, Spokane, WA, 99202-2131, USA

    Kara R. Vogel & K. Michael Gibson

  2. Department of Neurology, Children’s National Medical Center and the George Washington University School of Medicine, Washington, DC, USA

    Phillip L. Pearl

  3. Section of Clinical Epilepsy, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD, USA

    William H. Theodore

  4. Department of Epidemiology and Biostatistics, Children’s Research Institute, Children’s National Medical Center and the George Washington University School of Medicine, Washington, DC, USA

    Robert C. McCarter

  5. Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands

    Cornelis Jakobs

Authors
  1. Kara R. Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Phillip L. Pearl
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. William H. Theodore
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Robert C. McCarter
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cornelis Jakobs
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. K. Michael Gibson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Kara R. Vogel or K. Michael Gibson.

Additional information

Communicated by: Verena Peters

Rights and permissions

Reprints and permissions

About this article

Cite this article

Vogel, K.R., Pearl, P.L., Theodore, W.H. et al. Thirty years beyond discovery—Clinical trials in succinic semialdehyde dehydrogenase deficiency, a disorder of GABA metabolism. J Inherit Metab Dis 36, 401–410 (2013). https://doi.org/10.1007/s10545-012-9499-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10545-012-9499-5

Keywords

Search

Navigation