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Abstract
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Mutations in the Branched Chain α-Keto acid Dehydrogenase Kinase (BCKDK) gene have been linked to a potentially diet-responsive form of Autism Spectrum Disorder (ASD). Patients with BCKDK deficiency present with neurodevelopmental issues, including intellectual disability, ASD, and seizures, associated with low branched-chain amino acid (BCAA) levels. However, findings on BCAA levels in ASD remain inconsistent, requiring further research.
This case report describes a 4.5-year-old male with BCKDK deficiency and ASD. The patient initially presented with diarrhea, foul-smelling stools, abdominal pain, and recurrent infections, leading to a referral to the Inborn Errors of Metabolism Clinic. Metabolic testing revealed reduced valine, leucine, and isoleucine levels. Whole-exome sequencing (WES) confirmed a homozygous BCKDK mutation. A high-protein diet with BCAA supplementation was initiated, guided by plasma amino acid levels. The patient was later referred to child psychiatry clinic due to comorbid ASD. Clinical evaluation revealed limited eye contact, absence of meaningful speech, stereotypic behaviors, and intense interest in spinning objects. His CARS score was 42 (severe ASD). Developmental assessment using the Denver Test-II identified global developmental delays. After 4 months of dietary therapy, the mother reported improvements in joint attention. However, the CARS score showed a slight decrease to 40. The patient is being closely monitored with frequent follow-ups to assess both BCAA levels and autism severity, ensuring timely adjustments to dietary and therapeutic interventions as necessary.
In the literature, it has been reported that patients who started treatment before the age of 2 years did not develop autism, and patients who received early diagnosis and treatment (8 months) showed normal cognition and almost normal global neurodevelopment. However, in our case, despite achieving metabolic improvements through an appropriate dietary regimen, no significant reduction was observed in the CARS score, which assesses the severity of autism. This lack of improvement in ASD symptoms may be attributed to the relatively late initiation of dietary therapy at 4.5 years of age. Given the potential for ASD symptoms in these cases to be preventable or treatable, early diagnosis and prompt initiation of dietary treatment are critical. Recognizing and managing these cases at the earliest possible stage could provide better outcomes for ASD prognosis.
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