A possible biomarker of neurocytolysis in infantile gangliosidoses: aspartate transaminase

  • Mustafa KılıçEmail author
  • Çiğdem Seher Kasapkara
  • Sebile Kılavuz
  • Neslihan Önenli Mungan
  • Gürsel Biberoğlu
Original Article


Gangliosidoses (GM1 and GM2 gangliosidosis) are rare, autosomal recessive progressive neurodegenerative lysosomal storage disorders caused by defects in the degradation of glycosphingolipids. We aimed to investigate clinical, biochemical and molecular genetic spectrum of Turkish patients with infantile gangliosidoses and examined the potential role of serum aspartate transaminase levels as a biomarker. We confirmed the diagnosis of GM1 and GM2 gangliosidosis based on clinical findings with specific enzyme and/or molecular analyses. We retrospectively reviewed serum aspartate transaminase levels of patients with other biochemical parameters. Serum aspartate transaminase level was elevated in all GM1 and GM2 gangliosidosis patients in whom the test was performed, along with normal alanine transaminase. Aspartate transaminase can be a biochemical diagnostic clue for infantile gangliosidoses. It might be a simple but important biomarker for diagnosis, follow up, prognosis and monitoring of the response for the future therapies in these patients.


GM1-gangliosidosis Tay-Sachs disease Sandhoff disease Aspartate transaminase Aspartate aminotransferase Biomarker 



We sincerely thank the family of the patient for their participation, after informed consent. We also thank to Prof. Erdem Karabulut for statistical contributions.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The study protocol was approved by the Medical Ethics Committee of Kecioren Training and Research Hospital.


  1. Aronson SM, Saifer A, Kanof A, Volk BW (1958) Progression of amaurotic family idiocy as reflected by serum and cerebrospinal fluid changes. Am J Med 24:390–401CrossRefGoogle Scholar
  2. Aronson SM, Saifer A, Perle G, Volk BW (1961) Studies on enzyme alterations in the infantile sphingolipidoses. Correlation with pathological changes. Am J Clin Nutr 9:103CrossRefGoogle Scholar
  3. Bradbury AM, Gray-Edwards HL, Shirley JL, McCurdy VJ, Colaco AN, Randle AN, Christopherson PW, Bird AC, Johnson AK, Wilson DU, Hudson JA, de Pompa NL, Sorjonen DC, Brunson BL, Jeyakumar M, Platt FM, Baker HJ, Cox NR, Sena-Esteves M, Martin DR (2015) Biomarkers for disease progression and AAV therapeutic efficacy in feline Sandhoff disease. Exp Neurol 263:102–112. CrossRefPubMedGoogle Scholar
  4. Gray-Edwards HL, Regier DS, Shirley JL, Randle AN, Salibi N, Thomas SE, Latour YL, Johnston J, Golas G, Maguire AS, Taylor AR, Sorjonen DC, McCurdy VJ, Christopherson PW, Bradbury AM, Beyers RJ, Johnson AK, Brunson BL, Cox NR, Baker HJ, Denney TS, Sena-Esteves M, Tifft CJ, Martin DR (2017a) Novel biomarkers of human GM1 Gangliosidosis reflect the clinical efficacy of gene therapy in a feline model. Mol Ther 25:892–903. CrossRefPubMedPubMedCentralGoogle Scholar
  5. Gray-Edwards HL, Jiang X, Randle AN, Taylor AR, Voss TL, Johnson AK, McCurdy VJ, Sena-Esteves M, Ory DS, Martin DR (2017b) Lipidomic evaluation of feline neurologic disease after AAV gene therapy. Mol Ther Methods Clin Dev 6:135–142. CrossRefPubMedPubMedCentralGoogle Scholar
  6. Gray-Edwards HL, Randle AN, Maitland SA, Benatti HR, Hubbard SM, Canning PF, Vogel MB, Brunson BL, Hwang M, Ellis LE, Bradbury AM, Gentry AS, Taylor AR, Wooldridge AA, Wilhite DR, Winter RL, Whitlock BK, Johnson JA, Holland M, Salibi N, Beyers RJ, Sartin JL, Denney TS, Cox NR, Sena-Esteves M, Martin DR (2018) Adeno-associated virus gene therapy in a sheep model of Tay-Sachs disease. Hum Gene Ther 29:312–326. CrossRefPubMedGoogle Scholar
  7. Kodama T, Togawa T, Tsukimura T, Kawashima I, Matsuoka K, Kitakaze K, Tsuji D, Itoh K, Ishida YI, Suzuki M, Suzuki T, Sakuraba H (2011) Lyso-GM2 ganglioside: a possible biomarker of Tay-Sachs disease and Sandhoff disease. PLoS One 6:e29074. CrossRefPubMedPubMedCentralGoogle Scholar
  8. Kresse H, Fuchs W, Glössl J, Holtfrerich D, Gilberg W (1981) Liberation of N-acetylglucosamine-6-sulfate by human beta-N-acetylhexosaminidase a. J Biol Chem 256:12926–12932PubMedGoogle Scholar
  9. Lee JS, Choi JM, Lee M, Kim SY, Lee S, Lim BC, Cheon JE, Kim IO, Kim KJ, Choi M, Seong MW, Chae JH (2018) Diagnostic challenge for the rare lysosomal storage disease: late infantile GM1 gangliosidosis. Brain Dev 40:383–390CrossRefGoogle Scholar
  10. Lending M, Slobody LB, Stone MD, Hosback RE, Mestem J (1959) Activity of glutamic oxalacetic transaminase and lactic dehydrogenase in cerebrospinal fluid and plasma of normal and abnormal newborn infants. Pediatrics 24:378PubMedGoogle Scholar
  11. McCurdy VJ, Johnson AK, Gray-Edwards HL et al (2014) Sustained normalization of neurological disease after intracranial gene therapy in a feline model. Sci Transl Med 6:231ra48. CrossRefPubMedPubMedCentralGoogle Scholar
  12. Osmon KJ, Woodley E, Thompson P et al (2016) Systemic gene transfer of a Hexosaminidase variant using an scAAV9.47 vector corrects GM2 Gangliosidosis in Sandhoff mice. Hum Gene Ther 27:497–508. CrossRefPubMedGoogle Scholar
  13. Satoh H, Yamato O, Asano T, Yonemura M, Yamauchi T, Hasegawa D, Orima H, Arai T, Yamasaki M, Maede Y (2007) Cerebrospinal fluid biomarkers showing neurodegeneration in dogs with GM1 gangliosidosis: possible use for assessment of a therapeutic regimen. Brain Res 1133:200–208CrossRefGoogle Scholar
  14. Schneck L, Maisel J, Volk BW (1964) The startle response and serum enzyme profile in early detectıon of Tay-Sachs' disease. J Pediatr 65:749–756CrossRefGoogle Scholar
  15. Takamura A, Higaki K, Kajimaki K, Otsuka S, Ninomiya H, Matsuda J, Ohno K, Suzuki Y, Nanba E (2008) Enhanced autophagy and mitochondrial aberrations in murine G(M1)-gangliosidosis. Biochem Biophys Res Commun 367:616–622. CrossRefPubMedGoogle Scholar
  16. Utz JR, Crutcher T, Schneider J, Sorgen P, Whitley CB (2015) Biomarkers of central nervous system inflammation in infantile and juvenile gangliosidoses. Mol Genet Metab 114:274–280. CrossRefPubMedGoogle Scholar
  17. Vanier MT, Caillaud C, Levade T (2016) Sphingolipidosis. In: Saudubray JM, Baumgartner MR, Walter J (eds) Inborn metabolic diseases, diagnosis and treatment, 6 th edn. Springer, Berlin, Heidelberg, pp 556–566Google Scholar
  18. Volk BW, Aronson SM, Saifer A (1964) Fructose-1 phosphate aldolase deficiency in Tay-Sachs disease. Am J Med 36:481–484CrossRefGoogle Scholar
  19. Wenger DA, Williams C (1991) Screening for lysosomal disorders. In: Hommes FA, editor. Techniques in diagnostic human biochemical genetics: a laboratory manual. New York, NY: Wiley-Liss, pp587–617.Google Scholar
  20. Yamato O, Satoh H, Matsuki N, Ono K, Yamasaki M, Maade Y (2004) Laboratory diagnosis of canine GM2-gangliosidosis using blood and cerebrospinal fluid. J Vet Diagn Investig 16:39–44CrossRefGoogle Scholar

Copyright information

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

Authors and Affiliations

  • Mustafa Kılıç
    • 1
    Email author
  • Çiğdem Seher Kasapkara
    • 1
  • Sebile Kılavuz
    • 2
  • Neslihan Önenli Mungan
    • 2
  • Gürsel Biberoğlu
    • 3
  1. 1.Metabolism UnitSami Ulus Children HospitalAnkaraTurkey
  2. 2.Department of Pediatrics, Metabolism UnitCukurova UniversityAdanaTurkey
  3. 3.Department of Pediatrics, Metabolism UnitGazi UniversityAnkaraTurkey

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