Inborn Errors of Metabolism Associated With Autism Among Children: A Multicenter Study from Iran

Area of Science:

• Medical Genetics
• Neurodevelopmental Disorders
• Metabolic Disorders

Background:

• Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with diverse etiologies.
• Inborn errors of metabolism (IEMs) are increasingly recognized as potential contributing factors in some individuals with ASD.
• Identifying IEMs in ASD patients can inform targeted interventions and genetic counseling.

Purpose of the Study:

• To investigate the prevalence and types of common inborn errors of metabolism in Iranian children and adolescents diagnosed with autism spectrum disorder.
• To identify clinical and demographic factors associated with positive metabolic screening results in this population.

Main Methods:

• A cross-sectional, multicenter study involving 105 Iranian children and adolescents with ASD.
• Comprehensive metabolic screening including plasma amino acids, acylcarnitines, creatine, guanidinoacetate, and urinary organic acids, purines, and pyrimidines.
• Data collection on age, parental consanguinity, seizure history, developmental milestones, and physical examination.

Main Results:

• Inborn errors of metabolism were detected in 13 (12.4%) of the participants.
• Identified IEMs included cerebral creatine deficiency syndrome (4.8%), arginine succinate aciduria (3.8%), 2-methylbutyryl glycinuria, short-chain acyl-CoA dehydrogenase deficiency, and combined methylmalonic aciduria/malonic aciduria.
• Positive metabolic findings were strongly associated with parental consanguinity, a history of seizures, microcephaly, and delayed development.

Conclusions:

• Metabolic screening is recommended for Iranian ASD patients, especially those with parental consanguinity, developmental delay, and a history of seizures.
• A suggested screening panel includes plasma amino acids, acylcarnitines, creatine, guanidinoacetate, and urinary organic acids.
• Early identification of IEMs can potentially lead to improved management strategies for individuals with autism spectrum disorder.