A potential pathogenic role of oxalate in autism

Konstantynowicz, Jerzy; Porowski, Tadeusz; Zoch-Zwierz, W; Wasilewska, Jolanta; Kądziela-Olech, Halina; Kułak, Wojciech; Owens, Susan Costen; Piotrowska-Jastrzębska, Janina; Kaczmarski, Maciej

doi:10.1016/j.ejpn.2011.08.004

Cited by 36 publications

(34 citation statements)

References 50 publications

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“…Interestingly, along with the typical behavioral and communication issues, gastrointestinal symptoms often exist in children with ASD (6, 7). This observation could indicate that a more complex and global metabolic disorder exists.…”

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confidence: 99%

“…Providing some scientific support for the involvement of oxalate in ASD is a study showing that children with ASD displayed a 3-fold increase in plasma oxalate levels compared to age and gender matched controls (7). Nevertheless, the precise molecular origin and potential effect of hyperoxalemia in children with ASD remains unclear.…”

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confidence: 99%

“…The reports that: (1) Plasma oxalate levels in children with ASD tend to be high (7); (2) The prevalence of iron-refractory ID/IDA in children with ASD is high (10–13, 15); (3) Children with ASD have gastrointestinal problems that could affect both iron and oxalate uptake in the gut (6); and (4) hTF/2N (OX) and Fe 2 hTF (OX) do not readily relinquish iron (38) collectively suggest a potential link between oxalate and iron deficiency anemia in autism. Thus, high plasma oxalate levels and iron-refractory ID/IDA in children with ASD might be mediated via hTF (OX) .…”

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confidence: 99%

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Human Serum Transferrin: Is There a Link among Autism, High Oxalate Levels, and Iron Deficiency Anemia?

Luck

Bobst²,

Kaltashov³

et al. 2013

Biochemistry

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It has been previously suggested that high amounts of oxalate in plasma could play a role in autism by binding to the bilobal iron transport protein transferrin (hTF) thereby interfering with iron metabolism by inhibiting iron delivery to cells. By examining the effect of the substitution of oxalate for the physiologically utilized synergistic carbonate anion in each lobe of hTF we sought to provide a molecular basis for or against such a role. Our work clearly shows both qualitatively (6 M urea gels) and quantitatively (kinetic analysis by stop flow spectrofluorimetry) that the presence of oxalate in place of carbonate in each binding site of hTF does indeed greatly interfere with iron removal from each lobe (both in the absence and presence of the specific hTF receptor). However, we also clearly demonstrate that once the iron is bound within each lobe of hTF, neither anion can displace the other. Additionally, as verified by urea gels and electrospray mass spectrometry, formation of completely homogeneous hTF-anion complexes requires that all iron must first be removed and hTF then reloaded with iron in the presence of either carbonate or oxalate. Of significance, experiments described herein show that carbonate is the preferred binding partner, i.e., even if an equal amount of each anion is available during the iron loading process the hTF-carbonate complex is formed.

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Human Serum Transferrin: Is There a Link among Autism, High Oxalate Levels, and Iron Deficiency Anemia?

Luck

Bobst²,

Kaltashov³

et al. 2013

Biochemistry

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“…1,2 Systemic accumulation culminating in excessive plasma and/or urine oxalate levels occurs in a variety of disease states, including genetic deficiencies of oxalate liver metabolism, 2 chronic renal failure, 3 calcium oxalate nephrolithiasis, 4 malabsorptive states such as cystic fibrosis 5 or Roux-en-Y gastric bypass surgery, 6 and perhaps even autism. 7 Because of increased awareness of oxalate-based diseases and prevalence of nephrolithiasis in the United States, 8 there is an increasing need for simple, rapid assays that provide temporal-based monitoring of oxalate levels in urine and/or blood. Current methods for determining oxalate, however, are complex, labor intensive, and require a color spectrophotometer or ion chromatograph found only in laboratory settings.…”

Section: Introductionmentioning

confidence: 99%

Rapid Oxalate Determination in Blood and Synthetic Urine Using a Newly Developed Oxometer

Canales

Richards

Peck

2013

Journal of Endourology

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Blood and urine oxalate determinations have been limited to the laboratory setting because of complex sample storage and processing methods as well as the need for color spectrophotometry and ion chromatography. We hypothesized that glucometer test strips, impregnated with glucose oxidase and dyes that measure secondary hydrogen peroxide production, could be infused with oxalate oxidase and produce enhanced color changes in the presence of oxalate. By increasing the amount of sodium oxalate in fresh blood, we found that glucometer-measured oxalate increased on a linear scale. In addition, oxalate levels in synthetic urine could be measured using a visual scale, suggesting that strip dwell time or oxalate/oxalate oxidase concentrations could be manipulated to enhance optimal sensitivity. Although further testing is necessary, this simple, first-generation oxometer may eventually allow point of care testing in the home or office, empowering patients with oxalate-based medical conditions and giving healthcare providers real-time oxalate feedback.

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“…A low-oxalate diet has been recommended for children with ASD (40-50 mg per day) based on one study in patients with ASD showing higher plasma oxalate and urine oxalate levels [46].…”

Section: Special Dietsmentioning

confidence: 99%

Pharmacobiological Treatments in Autism Spectrum Disorders

Jayaraman¹,

Mundkur²

2017

IJCRR

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Autism spectrum disorders (ASD) refer to a group of neuro-developmental disorders affecting young children and adults. Currently, the treatment options for ASD are mostly restricted to treating its symptoms. Among the various approaches for treating ASD, pharmacobiology-based treatments are numerous. Our objective is to review the up-to-date information on different types of medications and briefly discuss the evidence-based potential of these treatments in ASD therapy. PubMed searches for reports and reviews on clinical data from the last 15 years, between 2002-2017, using search terms of each category of treatment along with the terms "autism", "mechanism", and/or "side effects" were conducted. Several pharmacobiological interventions have been prescribed for ASD, including antipsychotics, stimulants, antidepressants, supplements, and special diets. However, none of these methods is an effective ASD treatment, and only few show much promise. We provide a brief overview of the current pharmacobiological treatments for ASD, their mechanisms of action, and clinical research-based evidence on their effectiveness. Based on our review, we recommend that caution should be exercised when choosing a pharmacobiological treatment method for ASD as majority of existing evidence is not from large-scale long-term high quality studies.Future research should focus on rigorous investigative design, long-term implementation, and meaningful uniform outcome measurements.

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A potential pathogenic role of oxalate in autism

Cited by 36 publications

References 50 publications

Human Serum Transferrin: Is There a Link among Autism, High Oxalate Levels, and Iron Deficiency Anemia?

Human Serum Transferrin: Is There a Link among Autism, High Oxalate Levels, and Iron Deficiency Anemia?

Rapid Oxalate Determination in Blood and Synthetic Urine Using a Newly Developed Oxometer

Pharmacobiological Treatments in Autism Spectrum Disorders

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