Published online Jun 9, 2026. doi: 10.5409/wjcp.v15.i2.112164
Revised: August 16, 2025
Accepted: November 25, 2025
Published online: June 9, 2026
Processing time: 298 Days and 11 Hours
The identification of bioindicators for the detection and monitoring of autism spectrum disorder (ASD) still remains a major challenge in clinical medicine. The protein klotho has been linked to various neurological disorders.
To investigate the evaluation of soluble alpha-klotho (S-KLα) as a new indicator for the diagnosis and monitoring of patients with ASD. This study was conducted in the absence of any prior studies or research on the link between klotho and ASD, nor on how it affects the characteristics of those impacted. To address this gap, we considered this study.
The case-control study involved 256 individuals of both sexes, aged between 2 years and 15 years, divided into two groups: 156 children with ASD from autism centers in Dohuk and Zakho cities, Kurdistan Region/Iraq, and 100 healthy individuals serving as the control group. Serum S-KLα level was measured using enzyme-linked immunosorbent assay. Additionally, levels of hemoglobin, iron, glucose, uric acid, creatinine, and vitamin D3 were estimated, with all measure
The results showed a significant decrease in S-KLα levels in the sera of patients with ASD (97.5 ± 19.6) compared to the control group (133.7 ± 32.4). Additionally, the area under the curve (0.91) from the receiver operating characteristic analysis confirms the potential of using S-KLα as a marker for ASD. Furthermore, a notable decline in S-KLα was observed with increasing age, and higher levels of S-KLα were found in girls compared to boys, in both the control and patient groups (P < 0.001). The S-KLα levels in patients with ASD were not influenced by family history or birth weight. However, a significant reduction was seen in patients who experienced a difficult birth (dystocia), as well as in preterm births (< 37 weeks) and post-term births (> 42 weeks). It was observed that there was a significantly negative correlation between S-KLα and glucose level. By contrast, positive correlations were found with hemoglobin, iron, and vitamin D3 (P < 0.01); however, no relationship was detected with creatinine and uric acid levels in patients with ASD.
This is the first case-control study to confirm the strong potential of serum S-KLα as a predictive biomarker in autism risk profiling. The proposals outlined by the study suggest new directions and strategies for future research, linking klotho as a potential diagnostic marker for ASD and its complications, as well as its possible role as a therapeutic target.
Core Tip: This is the first study to examine the relationship between soluble alpha-klotho (S-KLα) and autism spectrum disorder (ASD). It involves two groups aged 2-15 years: One healthy group and another comprising patients from autism centers in the Kurdistan Region, Iraq. We compared these groups and analyzed risk factors associated with ASD. The results showed a significant reduction in S-KLα levels in the sera of patients with ASD. S-KLα levels were affected by several risk factors and demonstrated a significant correlation with multiple clinical markers, suggesting a role for S-KLα in ASD and as a predictive biomarker in ASD risk assessment.