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Journal of Inherited Metabolic Disease

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29.09.2016 | Rapid Communication

Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism

verfasst von: E. E. Jansen, K. R. Vogel, G. S. Salomons, P. L. Pearl, J.-B. Roullet, K. M. Gibson

Erschienen in: Journal of Inherited Metabolic Disease | Ausgabe 6/2016

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Abstract

We hypothesized that blood levels of γ-aminobutyric acid (GABA) and γ-hydroxybutyric acid (GHB), biomarkers of succinic semialdehyde dehydrogenase deficiency (SSADHD), would correlate with age. GABA and GHB were quantified in plasma and red blood cells (RBCs) from 18 patients (age range 5–41 years; median 8). Both metabolites negatively correlated with age (P < 0.05). Plasma and RBC GHB declined with age, reaching a nadir and approximate steady state by 10 years. Declining plasma GABA achieved this approximate steady state at 30–40 years of age. These biomarker relationships may reflect further GABA- and GHB-ergic neurotransmission imbalances that correlate with the onset of adolescent/adulthood neuropsychiatric morbidity and epilepsy in SSADHD.

Bjork JM, Moeller FG, Kramer GL et al (2001) Plasma GABA levels correlate with aggressiveness in relatives of patients with unipolar depressive disorder. Psychiatry Res 101(2):131–136CrossRefPubMed

Buzzi A, Wu Y, Frantseva MV et al (2006) Succinic semialdehyde dehydrogenase deficiency: GABAB receptor-mediated function. Brain Res 1090(1):15–22CrossRefPubMed

Casado M, Molero M, Sierra C, Garcia-Cazorla A, Ormazabal A, Artuch R (2014) Analysis of cerebrospinal fluid γ-aminobutyric acid by capillary electrophoresis with laser-induced fluorescence detection. Electrophoresis 35:1181–1187CrossRefPubMed

Forni S, Pearl PL, Gibson KM et al (2013) Quantitation of gamma-hydroxybutyric acid in dried blood spots: feasibility assessment for newborn screening of succinic semialdehyde dehydrogenase (SSADH) deficiency. Mol Genet Metab 109(3):255–259CrossRefPubMed

Gibson KM, Aramaki S, Sweetman L et al (1990) Stable isotope dilution analysis of 4-hydroxybutyric acid: an accurate method for quantification in physiological fluids and the prenatal diagnosis of 4-hydroxybutyric aciduria. Biomed Environ Mass Spectrom 19(2):89–93CrossRefPubMed

Gibson KM, Jakobs C, Ogier H et al (1995) Vigabatrin therapy in six patients with succinic semialdehyde dehydrogenase deficiency. J Inherit Metab Dis 18(2):143–146CrossRefPubMed

Gibson KM, Gupta M, Pearl PL et al (2003) Significant behavioral disturbances in succinic semialdehyde dehydrogenase (SSADH) deficiency (gamma-hydroxybutyric aciduria). Biol Psychiatry 54(7):763–768CrossRefPubMed

Jakobs C, Bojasch M, Mönch E et al (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(2–3):169–178CrossRefPubMed

Jansen EE, Struys E, Jakobs C et al (2008) Neurotransmitter alterations in embryonic succinate semialdehyde dehydrogenase (SSADH) deficiency suggest a heightened excitatory state during development. BMC Dev Biol 8:112CrossRefPubMedPubMedCentral

Knerr I, Pearl PL, Bottiglieri T et al (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(3):279–294CrossRefPubMed

Knerr I, Gibson KM, Murdoch G et al (2010) Neuropathology in succinic semialdehyde dehydrogenase deficiency. Pediatr Neurol 42(4):255–258CrossRefPubMedPubMedCentral

Kok RM, Howells DW, van den Heuvel CC et al (1993) Stable isotope dilution analysis of GABA in CSF using simple solvent extraction and electron-capture negative-ion mass fragmentography. J Inherit Metab Dis 16(3):508–512CrossRefPubMed

Kowa H, Shimomura T, Takahashi K (1992) Platelet gamma-aminobutyric acid levels in migraine and tension-type headache. Headache 32:229–232CrossRefPubMed

Lanctot KL, Herrmann N, Rothenburg L, Eryavec G (2007) Behavioral correlates of GABAergic disruption in Alzheimer’s disease. Int Psychogeriatr 19(1):151–158CrossRefPubMed

Lapalme-Remis S, Lewis EC, De Meulemeester C et al (2015) Natural history of succinic semialdehyde dehydrogenase deficiency through adulthood. Neurology 85(10):861–865CrossRefPubMedPubMedCentral

Maitre M, Klein C, Mensah-Nyagan AG (2016) Mechanisms for the specific properties of γ-hydroxybutyrate in brain. Med Res Rev 36(3):363–388CrossRefPubMed

Malaspina P, Roullet J-B, Pearl PL et al (2016) Succinic semialdehyde dehydrogenase deficiency (SSADHD): pathophysiological complexity and multifactorial trait associations in a rare monogenic disorder of GABA metabolism. Neurochem. Intl., available on-line June 14

Novotny EJ Jr, Fulbright RK, Pearl PL et al (2003) Magnetic resonance spectroscopy of neurotransmitters in human brain. Ann Neurol 54(Suppl 6):S25–S31CrossRefPubMed

Parviz M, Vogel K, Gibson KM, Pearl PL (2014) Disorders of GABA metabolism: SSADH and GABA-transaminase deficiencies. J Pediatr Epilepsy 3(4):217–227CrossRefPubMedPubMedCentral

Pearl PL, Gibson KM, Quezado Z et al (2009) Decreased GABA-A binding on FMZ-PET in succinic semialdehyde dehydrogenase deficiency. Neurology 73(6):423–429CrossRefPubMedPubMedCentral

Pearl PL, Schreiber J, Theodore WH et al (2014) Taurine trial in succinic semialdehyde dehydrogenase deficiency and elevated CNS GABA. Neurology 82(11):940–944CrossRefPubMedPubMedCentral

Reis J, Cohen LG, Pearl PL et al (2012) GABAB-ergic motor cortex dysfunction in SSADH deficiency. Neurology 79(1):47–54CrossRefPubMedPubMedCentral

Talaei SA, Azami A, Salami M (2016) Postnatal development and sensory experience synergistically underlie the excitatory/inhibitory features of hippocampal neural circuits: glutamatergic and GABAergic neurotransmission. Neuroscience 318:230–243CrossRefPubMed

Therrell BL, Padilla CD, Loeber JG et al (2015) Current status of newborn screening worldwide: 2015. Semin Perinatol 39(3):171–187CrossRefPubMed

Vogel KR, Ainslie GR, Jansen EEW, Salomons GS, Gibson KM Therapeutic relevance of mTOR inhibition in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. Biochim Biophys Acta, in revision

Vogel KR, Ainslie GR, Gibson KM (2016) mTOR inhibitors rescue premature lethality and attenuate dysregulation of GABAergic/glutamatergic transcription in murine succinate semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism. J Inherit Metab Dis. doi:10.1007/s10545-016-9959-4

Titel: Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism
verfasst von: E. E. Jansen
K. R. Vogel
G. S. Salomons
P. L. Pearl
J.-B. Roullet
K. M. Gibson
Publikationsdatum: 29.09.2016
Verlag: Springer Netherlands
Erschienen in: Journal of Inherited Metabolic Disease / Ausgabe 6/2016
Print ISSN: 0141-8955
Elektronische ISSN: 1573-2665
DOI: https://doi.org/10.1007/s10545-016-9980-7

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Correlation of blood biomarkers with age informs pathomechanisms in succinic semialdehyde dehydrogenase deficiency (SSADHD), a disorder of GABA metabolism

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