Blood Lead Level, Urinary Porphobilinogen and Serum Acetylcholine in Nigerian Children with Autism Spectrum Disorder: A Case-Control Study

Authors

  • Mudathir Adebusuyi Adewole Author
  • Ayodeji Oladeji Olanrewaju Author
  • Ishiaq Olayinka Omotosho Author
  • Yetunde C. Adeniyi Author

DOI:

https://doi.org/10.54878/4mzxpg10

Keywords:

Autism spectrum disorder, neurodevelopment disorder, heavy metal toxicity, blood lead level, serum acetylcholine

Abstract

Purpose: Autism spectrum disorder (ASD), a common neurodevelopmental disorder characterized by communication and behavioral deficits, remains a subject of unknown etiology. However, the interplay of heavy metal toxicity and altered neurotransmission have been implicated in the development of ASD. Therefore, this study examined blood lead level (BLL), serum acetylcholine (ACh), and urine porphobilinogen (PBG) levels in Nigerian children with ASD. Methods: Forty participants aged 3 to 12 years were recruited, including 14 children diagnosed with ASD (cases), 13 children with neurodevelopmental disorders (NDDs) excluding ASD (positive controls), and 13 neurotypical children (negative controls). BLL was measured using atomic absorption spectroscopy (AAS), while serum ACh and urinary PBG levels were assessed using ELISA and modified Mauzerall-Granick methods, respectively. Results: The study revealed no significant difference in BLL between the cases and controls. However, urinary PBG levels were significantly higher cases (4.03 ± 0.57 µmol/mmol creatinine) compared to negative controls (3.29 ± 0.46 µmol/mmol creatinine). Additionally, the study found significantly lower serum ACh levels in the cases (588.55 ± 239.09 pg/mL) and positive controls (439.10 ± 260.69 pg/mL) compared to the negative controls (843.19 ± 339.63 pg/mL). Importantly, no significant correlation was found between BLL, PBG, and ACh. Conclusion: The study findings suggest potential chronic metal toxicity and altered cholinergic neurotransmission may play a role in the etiology of ASD. Further research is needed to explore the specific mechanism.

References

Arnold, H., Burk, J., Hodgson, E., Sarter, M., & Bruno, J. (2002). Differential cortical acetylcholine release in rats performing a sustained attention task versus behavioral control tasks that do not explicitly tax attention. Neuroscience, 114(2), 451-460.

Austin, D. W., & Shandley, K. (2008). An investigation of porphyrinuria in Australian children with autism. Journal of Toxicology and Environmental Health, Part A, 71(20), 1349-1351.

Avale, M. E., Chabout, J., Pons, S., Serreau, P., De Chaumont, F., Olivo‐Marin, J. C., . . . Granon, S. (2011). Prefrontal nicotinic receptors control novel social interaction between mice. The FASEB Journal, 25(7), 2145-2155.

Bjørklund, G., Skalny, A. V., Rahman, M. M., Dadar, M., Yassa, H. A., Aaseth, J., . . . Tinkov, A. A. (2018a). Toxic metal (loid)-based pollutants and their possible role in autism spectrum disorder. Environmental research, 166, 234-250.

Bjørklund, G., Skalny, A. V., Rahman, M. M., Dadar, M., Yassa, H. A., Aaseth, J., . . . Tinkov, A. A. (2018b). Toxic metal(loid)-based pollutants and their possible role in autism spectrum disorder. Environmental Research, 166, 234-250. doi:https://doi.org/10.1016/j.envres.2018.05.020

Black, D. W., & Grant, J. E. (2014). DSM-5® guidebook: the essential companion to the diagnostic and statistical manual of mental disorders: American Psychiatric Pub.

Crook, M. (2013). Clinical biochemistry and metabolic medicine: CRC Press.

El-Ansary, A. K., Bacha, A. B., & Al-Ayahdi, L. Y. (2011). Relationship between chronic lead toxicity and plasma neurotransmitters in autistic patients from Saudi Arabia. J Clinical Biochemistry, 44(13), 1116-1120.

Engvall, E., & Perlmann, P. (1971). Enzyme-linked immunosorbent assay (ELISA). Quantitative assay of immunoglobulin G. Immunochemistry, 8(9), 871-874. doi:10.1016/0019-2791(71)90454-x

Feldman, D. S., Levere, R. D., Lieberman, J. S., Cardinal, R. A., & Watson, C. J. (1971). Presynaptic neuromuscular inhibition by porphobilinogen and porphobilin. Proc Natl Acad Sci U S A, 68(2), 383-386. doi:10.1073/pnas.68.2.383

Fido, A., & Al-Saad, S. (2005). Toxic trace elements in the hair of children with autism. Autism, 9(3), 290-298.

Friedman, S. D., Shaw, D. W., Artru, A. A., Dawson, G., Petropoulos, H., & Dager, S. R. (2006). Gray and white matter brain chemistry in young children with autism. Arch Gen Psychiatry, 63(7), 786-794. doi:10.1001/archpsyc.63.7.786

Geier, D. A., & Geier, M. R. (2006). A prospective assessment of porphyrins in autistic disorders: a potential marker for heavy metal exposure. Neurotoxicity Research, 10(1), 57-63.

Ghaleiha, A., Ghyasvand, M., Mohammadi, M.-R., Farokhnia, M., Yadegari, N., Tabrizi, M., . . . Akhondzadeh, S. (2014). Galantamine efficacy and tolerability as an augmentative therapy in autistic children: A randomized, double-blind, placebo-controlled trial. Journal of Psychopharmacology, 28(7), 677-685.

Gibson, S. L., Mackenzie, J., Goldberg, A. J. O., & Medicine, E. (1968). The diagnosis of industrial lead poisoning. 25(1), 40-51.

Gorini, F., Muratori, F., & Morales, M. A. (2014). The Role of Heavy Metal Pollution in Neurobehavioral Disorders: a Focus on Autism. Review Journal of Autism and Developmental Disorders, 1(4), 354-372. doi:10.1007/s40489-014-0028-3

Hamlin, J. C., Pauly, M., Melnyk, S., Pavliv, O., Starrett, W., Crook, T. A., & James, S. J. (2013). Dietary intake and plasma levels of choline and betaine in children with autism spectrum disorders. Autism Res Treat, 2013, 578429. doi:10.1155/2013/578429

Jaishankar, M., Tseten, T., Anbalagan, N., Mathew, B. B., & Beeregowda, K. N. (2014). Toxicity, mechanism and health effects of some heavy metals. Interdisciplinary toxicology, 7(2), 60-72. doi:10.2478/intox-2014-0009

Karvat, G., & Kimchi, T. (2014). Acetylcholine Elevation Relieves Cognitive Rigidity and Social Deficiency in a Mouse Model of Autism. Neuropsychopharmacology, 39(4), 831-840. doi:10.1038/npp.2013.274

Kawashima, K., Fujii, T., Misawa, H., Yamada, S., Tajima, S., Suzuki, T., . . . Kasahara, T. (1997). Presence of Acetylcholine in the Blood and its Production by Choline Acetyltransferase in Lymphocytes. In A. Teelken & J. Korf (Eds.), Neurochemistry: Cellular, Molecular, and Clinical Aspects (pp. 813-819). Boston, MA: Springer US.

Kern, J. K., Geier, D. A., Sykes, L., & Geier, M. (2014). Urinary porphyrins in autism spectrum disorders. In Comprehensive Guide to Autism (pp. 1333-1348): Springer New York New York, NY.

Lidsky, T. I., & Schneider, J. S. (2003). Lead neurotoxicity in children: basic mechanisms and clinical correlates. Brain, 126(1), 5-19.

Marotta, R., Risoleo, M. C., Messina, G., Parisi, L., Carotenuto, M., Vetri, L., & Roccella, M. (2020). The neurochemistry of autism. Brain sciences, 10(3), 163.

Mauzerall, D., & Granick, S. (1956). The occurrence and determination of delta-amino-levulinic acid and porphobilinogen in urine. J Biol Chem, 219(1), 435-446.

McDougle, C. J., Erickson, C. A., Stigler, K. A., & Posey, D. J. (2005). Neurochemistry in the pathophysiology of autism. Journal of Clinical Psychiatry, 66, 9.

Nataf, R., Skorupka, C., Amet, L., Lam, A., Springbett, A., & Lathe, R. (2006). Porphyrinuria in childhood autistic disorder: implications for environmental toxicity. Toxicology and Applied Pharmacology, 214(2), 99-108.

Nwobi, N. L., Adedapo, S. K., Olukolade, O., Oyinlade, O. A., Lagunju, I. A., Atulomah, N. O., . . . Anetor, J. I. (2019). Positive and inverse correlation of blood lead level with erythrocyte acetylcholinesterase and intelligence quotient in children: implications for neurotoxicity. J Interdisciplinary Toxicology, 12(3), 136-142.

Oflaherty, E. J. (1993). Physiologically based models for bone-seeking elements: IV. Kinetics of lead disposition in humans. Toxicology applied pharmacology, 118(1), 16-29.

Ohkawara, T., Katsuyama, T., Ida-Eto, M., Narita, N., Narita, M. J. B., & Development. (2015). Maternal viral infection during pregnancy impairs development of fetal serotonergic neurons. 37(1), 88-93.

Omotosho, I. O., Akinade, A., & Lagunju, I. (2018). Calcium and Magnesium Levels Are down Regulated in Nigerian Children with Autism Spectrum Disorder and Cerebral Palsy. Neuroscience and Medicine, 09, 159-170. doi:10.4236/nm.2018.93016

Ragozzino, M. E., Pal, S. N., Unick, K., Stefani, M. R., & Gold, P. E. (1998). Modulation of hippocampal acetylcholine release and spontaneous alternation scores by intrahippocampal glucose injections. Journal of neuroscience, 18(4), 1595-1601.

Reddy, G., & Zawia, N. J. I. (2000). Lead exposure alters Egr-1 DNA-binding in the neonatal rat brain. J International Journal of Developmental Neuroscience, 18(8), 791-795.

Ricci, A., Di Pierro, E., Marcacci, M., & Ventura, P. (2021). Mechanisms of Neuronal Damage in Acute Hepatic Porphyrias. Diagnostics (Basel), 11(12). doi:10.3390/diagnostics11122205

Rose, S., & Laan, M. J. (2009). Why match? Investigating matched case-control study designs with causal effect estimation. Int J Biostat, 5(1), Article 1. doi:10.2202/1557-4679.1127

Rosner, B. (2015). Fundamentals of biostatistics (8th ed.). Cengage learning

Schauder, A., Avital, A., & Malik, Z. (2010). Regulation and gene expression of heme synthesis under heavy metal exposure--review. J Environ Pathol Toxicol Oncol, 29(2), 137-158. doi:10.1615/jenvironpatholtoxicoloncol.v29.i2.70

Seethalakshmi. (2017). Neurotransmitters and their Impact on Mental Illness.

Toora, B. D., & Rajagopal, G. (2002). Measurement of creatinine by Jaffe's reaction--determination of concentration of sodium hydroxide required for maximum color development in standard, urine and protein free filtrate of serum. Indian J Exp Biol, 40(3), 352-354.

Wang, L., Almeida, L. E., Spornick, N. A., Kenyon, N., Kamimura, S., Khaibullina, A., . . . Quezado, Z. M. (2015). Modulation of social deficits and repetitive behaviors in a mouse model of autism: the role of the nicotinic cholinergic system. Psychopharmacology (Berl), 232(23), 4303-4316. doi:10.1007/s00213-015-4058-z

Woods, J. S. (1996). Altered porphyrin metabolism as a biomarker of mercury exposure and toxicity. Canadian journal of physiology and pharmacology, 74(2), 210-215.

Woods, J. S., Armel, S. E., Fulton, D. I., Allen, J., Wessels, K., Simmonds, P. L., . . . Rooney, J. P. (2010). Urinary porphyrin excretion in neurotypical and autistic children. Environ Health Perspect, 118(10), 1450-1457. doi:10.1289/ehp.0901713

Youn, S.-I., Jin, S.-H., Kim, S.-H., & Lim, S. (2010). Porphyrinuria in Korean children with autism: correlation with oxidative stress. Journal of Toxicology and Environmental Health, Part A, 73(10), 701-710.

Downloads

Published

2025-12-26

How to Cite

Adewole, M. A., Olanrewaju, A. O., Omotosho, I. O., & Adeniyi, Y. C. (2025). Blood Lead Level, Urinary Porphobilinogen and Serum Acetylcholine in Nigerian Children with Autism Spectrum Disorder: A Case-Control Study. International Journal for Autism Challenges & Solution, 2(2), 12-22. https://doi.org/10.54878/4mzxpg10