Prevalence and Types of Inborn Errors of Metabolism Among Children and Adolescents With Autism Spectrum Disorder at Kenyatta National Hospital

Abstract

Background: Autism affects about 1 in every 160 children globally. Genetic defects are associated with the development of Autism and about 10 to 20 % of these patients have genetic metabolic abnormalities. Involvement of the central nervous system in patients with Inborn Errors of Metabolism, result in neuropsychiatric manifestations including autism. Thus early detection and treatment of inborn errors of metabolism in patients with Autism is important for better management and improved outcomes. Study objectives: To determine the prevalence of Inborn Errors of Metabolism (IEMs) in children and adolescents with Autism spectrum disorder at Kenyatta National Hospital (KNH); to determine types of IEMs, and to describe the clinical characteristics of Autism Spectrum Disorder patients with Inborn Errors of Metabolism. Study design: This was a descriptive Cross-sectional study. Methodology: The study population comprised patients aged 18 months to 25 years with a clinical diagnosis of autism, on follow-up at the occupational therapy, neurology, and Psychiatry clinics at KNH. Consecutive sampling technique was used to recruit 78 study participants. Data was collected using an interviewer-administered questionnaire. A medical history and physical examination were done for each participant to obtain data on disease symptoms, treatment they are undergoing and relevant family history. Blood samples were then drawn and sent to Centogene Laboratory in Germany for genetic testing Data analysis: SPSS software was used for data analysis Continuous data was summarised using medians and Interquartile range, and categorical data summarized using frequencies and percentages. The prevalence of inborn errors of metabolism was calculated as a proportion and Binary logistic Regression analysis was used to assess for associations. p value < 0.05 was used to define significant associations. Results: Prevalence of Inborn errors of metabolism among children and adolescents with autism spectrum disorder at KNH was 14.1% 95%CI (7.3 - 23.8%). Metabolic disorders identified included Hunter syndrome 45.5% (n =5), Phenylketonuria 36.3% (n =4), Glycogen storage disorder 9.1% (n =1), and Methylmalonic aciduria with homocysteinemia at 9.1% (n =1). Clinical characteristics associated with presence of genetic mutations linked to Inborn Errors of metabolism were macrocephaly (OR =9.19, 95%CI:1.72 – 48.98, p =0.009), family history of autism (OR =2.71, 95%CI:1.34 – 14.32, p<0.001), and mental retardation (OR =4.13, 95%CI:2.11 – 15.74, p<0.001)were significantly associated with IEM. Genetic disorders such as autosomal dominant susceptibility to autism, Cornelia de Lange syndrome type 1 (CDLS), Intellectual developmental disorders, Bardet-Biedl syndrome type 19, Coffin-Siris syndrome-12 among others, were also found. Conclusion: There is high prevalence of IEMs among children and adolescents with Autism Spectrum Disorders at KNH and Hunter syndrome is the most common IEM reported among these children. Positive Family history of ASD, intellectual disability, macrocephaly, overweight, and musculoskeletal abnormalities showed a positive association with the presence of IEM among patients with ASD. Macrocephaly, family history of autism, mental retardation and seizures were associated with genetic mutations for IEMs among children. Recommendations: There is need to integrate early testing for enzyme deficiencies among children with autism spectrum disorders to guide better treatment approaches for improved outcomes