High levels of blood glutamic acid and ornithine in children with intellectual disability

Abstract

Objectives: Aminoacidopathies are inborn errors of metabolism (IEMs) that cause intellectual disability in children. Luckily, aminoacidopathies are potentially treatable, if diagnosed earlier in life. The focus of this study was the screening of aminoacidopathies in a cohort of patients suspected for IEMs.

Methods: Blood samples from healthy (IQ > 90; n = 391) and intellectually disabled (IQ < 70; n = 409) children (suspected for IEMs) were collected from different areas of Northern Punjab, Pakistan. An analytical HPLC assay was used for the screening of plasma amino acids.

Results: All the samples (n = 800) were analyzed on HPLC and forty-three out of 409 patient samples showed abnormal amino acid profiles mainly in the levels of glutamic acid, ornithine and methionine. Plasma concentration (Mean ± SD ng/mL) were significantly high in 40 patients for glutamic acid (patients: 165 ± 38 vs. controls: 57 ± 8, p < 0.00001) and ornithine (patients: 3177 ± 937 vs. controls: 1361 ± 91, p < 0.0001). Moreover, 3 patients showed abnormally high (53.3 ± 8.6 ng/mL) plasma levels of methionine.

Conclusion: In conclusion, biochemical analysis of samples from such patients at the metabolites level could reveal the underlying diseases which could be confirmed through advanced biochemical and genetic analyses. Thus, treatment to some of such patients could be offered. Thus burden of intellectual disability caused by such rare metabolic diseases could be reduced from the target populations.

Keywords:

• aminoacidopathies
• inborn errors of metabolism (IEMs)
• intellectual disability (ID)
• newborn screening (NBS)
• Pakistan

Disclosure statement

No potential conflict of interest was reported by the authors.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Additional information

Funding

This work was supported by the research project, “Diagnosis of treatable inborn metabolic disorders of intellectual disability” (Project No. CRP/PAK14-02; Contract No. CRP/14/012) funded by the International Centre for Genetic Engineering and Biotechnology (ICGEB), Italy. Moreover, Muhammad Wasim was funded by the High Education Commission (HEC), Islamabad, Pakistan by the Indigenous Ph.D. fellowship program.