Skip to main content
Log in

Plasma and Urinary Sulfate Determination in a Cohort with Autism

  • Published:
Biochemical Genetics Aims and scope Submit manuscript

Abstract

Sulfate is important for mammalian development but is not routinely measured in clinical settings. The renal NaS1 sulfate transporter maintains circulating sulfate levels and is linked to renal sulfate wasting in mice. Some autistic individuals exhibit renal sulfate wasting, but the etiology is yet unknown. We measured plasma and urinary sulfate levels, calculated the fractional excretion index (FEI) of sulfate, and screened for two loss-of-function NaS1 sequence variants (R12X and N174S) in 23 autistic individuals. The FEI sulfate values ranged from 0.13 to 0.50. NaS1 variants were detected in 18 of the 23 individuals (11 heterozygous N174S, four homozygous N174S, two heterozygous R12X, and one individual carried both R12X and N174S). Those individuals with neither sequence variant had FEI sulfate ≤ 0.34, whereas FEI sulfate ≥ 0.35 was found in about 60 % (11 of 18) of individuals that had R12X and/or N174S. This study links renal sulfate wasting with loss-of-function NaS1 sequence variants in humans.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

  • Adams JB, Audhya T, McDonough-Means S, Rubin RA, Quig D, Geis E, Gehn E, Loresto M, Mitchell J, Atwood S, Barnhouse S, Lee W (2011) Nutritional and metabolic status of children with autism vs. neurotypical children, and the association with autism severity. Nutr Metab 8:34

    Article  Google Scholar 

  • Ahmad M, Haque MF, Ahmad W, Abbas H, Haque S, Krakow D, Rimoin DL, Lachman RS, Cohn DH (1998) Distinct, autosomal recessive form of spondyloepimetaphyseal dysplasia segregating in an inbred Pakistani kindred. Am J Med Genet 78:468–473

    Article  PubMed  CAS  Google Scholar 

  • Alberti A, Pirrone P, Elia M, Waring R, Romano C (1999) Sulphation deficit in “low-functioning” autistic children: a pilot study. Biol Psychiatry 46:420–424

    Article  PubMed  CAS  Google Scholar 

  • Beck L, Markovich D (2000) The mouse Na+-sulfate cotransporter gene Nas1: cloning, tissue distribution, gene structure, chromosomal assignment, and transcriptional regulation by vitamin D. J Biol Chem 275:11880–11890

    Article  PubMed  CAS  Google Scholar 

  • Cole DE, Baldwin LS, Stirk LJ (1985) Increased renal reabsorption of inorganic sulfate in third-trimester high-risk pregnancies. Obstet Gynecol 66:485–490

    PubMed  CAS  Google Scholar 

  • Dawson PA (2011) Sulfate in fetal development. Semin Cell Dev Biol 22:653–659

    Article  PubMed  CAS  Google Scholar 

  • Dawson PA, Markovich D (2002) Transcriptional regulation of the sodium-sulfate cotransporter NaS(i)-1 gene. Cell Biochem Biophys 36:175–182

    Article  PubMed  CAS  Google Scholar 

  • Dawson PA, Markovich D (2007) Genetic polymorphisms of human sulfate transporters. Curr Pharmacogenomics 5:262–274

    Article  CAS  Google Scholar 

  • Dawson PA, Beck L, Markovich D (2003) Hyposulfatemia, growth retardation, reduced fertility and seizures in mice lacking a functional NaSi-1 gene. Proc Natl Acad Sci USA 100:13704–13709

    Article  PubMed  CAS  Google Scholar 

  • Dawson PA, Steane SE, Markovich D (2004) Behavioural abnormalities of the hyposulfataemic Nas1 knock-out mouse. Behav Brain Res 154:457–463

    Article  PubMed  CAS  Google Scholar 

  • Dawson PA, Steane SE, Markovich D (2005) Impaired memory and olfactory performance in NaSi-1 sulphate transporter deficient mice. Behav Brain Res 159:15–20

    Article  PubMed  CAS  Google Scholar 

  • Dawson PA, Huxley S, Gardiner B, Tran T, McAuley JL, Grimmond S, McGuchin MA, Markovich D (2009) Reduced mucin sulfonation and impaired intestinal barrier function in the hyposulfataemic NaS1 null mouse. Gut 58:910–919

    Article  PubMed  CAS  Google Scholar 

  • Dawson PA, Russell CS, Lee S, McLeay SC, van Dongen JM, Cowley DM, Clarke LA, Markovich D (2010) Urolithiasis and hepatotoxicity are linked to the anion transporter Sat1 in mice. J Clin Invest 120:702–712

    Article  Google Scholar 

  • Karniski LP, Lotscher M, Fucentese M, Hilfiker H, Biber J, Murer H (1998) Immunolocalization of sat-1 sulfate/oxalate/bicarbonate anion exchanger in the rat kidney. Am J Physiol 275:F79–F87

    PubMed  CAS  Google Scholar 

  • Lee A, Dawson PA, Markovich D (2005) NaSi-1 and Sat-1: structure, function and transcriptional regulation of two genes encoding renal proximal tubular sulfate transporters. Int J Biochem Cell Biol 37:1350–1356

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Dawson PA, Hewavitharana AK, Shaw PN, Markovich D (2006) Disruption of NaS1 sulfate transport function in mice leads to enhanced acetaminophen-induced hepatotoxicity. Hepatology 43:1241–1247

    Article  PubMed  CAS  Google Scholar 

  • Lee S, Kesby JP, Muslim MD, Steane SE, Eyles DW, Dawson PA, Markovich D (2007) Hyperserotonaemia and reduced brain serotonin levels in NaS1 sulphate transporter null mice. NeuroReport 18:1981–1985

    Article  PubMed  CAS  Google Scholar 

  • Noordam C, Dhir V, McNelis JC, Schlereth F, Hanley NA, Krone N, Meitink JAM, Smeets R, Sweep CGJ, Claahsen-van der Grinton HL, Arlt W (2009) Inactivating PAPSS2 mutations in a patient with premature pubarche. N Engl J Med 360:2310–2318

    Article  PubMed  CAS  Google Scholar 

  • Puche RC, Vaccaro D, Sanchez A, Gonzalez A, Sarano HD (1993) Increased fractional excretion of sulphate in stone formers. Br J Urol 71:523–526

    Article  PubMed  CAS  Google Scholar 

  • Waring RH, Ngong JM, Klovrza LV, Green S, Sharp H (1997) Biochemical parameters in autistic children. Dev Brain Dysfunct 10:40–43

    Google Scholar 

Download references

Acknowledgments

We would like to thank all patients for providing biological samples for this study. This study was supported by the Mater Children’s Hospital and the Mater Medical Research Institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Francis G. Bowling.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bowling, F.G., Heussler, H.S., McWhinney, A. et al. Plasma and Urinary Sulfate Determination in a Cohort with Autism. Biochem Genet 51, 147–153 (2013). https://doi.org/10.1007/s10528-012-9550-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10528-012-9550-0

Keywords

Navigation