Autism and Maple Syrup Urine Disease: A Case Report

Background: Autism is characterized by impairments in social interaction and communication and by restricted, repetitive, and stereotyped patterns of behavior. It is commonly accepted that the pathophysiology of autism is multifactorial. In most of the patients it is not possible to identify any etiological explanation in spite of extensive medical investigations. However, in about 10% of cases an associated medical condition is found. Maple syrup urine disease (MSUD) is a rare autosomal recessive metabolic disorder caused by a deficiency of the branched - chain 2 ketoacid dehydrogenase activity which leads to accumulation of toxic levels of  branched chain amino acids (leucine, valine and isoleucine) in tissues and body fluids. MSUD has been associated with central nervous system damage, developmental delay, and neurocognitive deficits.

Objectives: According to our knowledge there is no reported case with both autism and MSUD.

Methods: We describe occurrence of autism in a girl with MSUD.

Results: The case is a  62 - month - old girl of a consanguineous 27-year-old mother and 31-year-old father. She was referred to our clinic for her self-injurious behaviors, aggression and sleep problems. During her assessment she had poor eye contact and no joint attention. She did not show reciprocity during social interaction. She also had repetitive behaviors such as rocking her body and flapping her hands. Her motor development was delayed: she sat at 15 months and walked 24 months of age. She did not develop phrases and had only 10 single words.  She had grand mal epilepsy and was on oxcarbazepine treatment. She was diagnosed as MSUD when she was 15 months of age and was on special education for her intellectual disability. In her family history her aunt had mental retardation and her cousin (female) had a diagnosis of MSUD. According to her psychiatric evaluation she had a diagnosis of autism disorder and moderate mental retardation. Childhood Autism Rating Scale and Autism Behaviour Checklist (ABC) were used to rate the severity of her autistic symptoms. Her ABC score was 93 and in CARS she had 48 that means high severity of autism symptoms.

Conclusions: Although a chance occurrence of these two conditions can not be ruled out, it is possible that MSUD might have played a role in the emergence of AD in this reported case. Studies on rats showed that alpha-keto acids accumulating in maple syrup urine disease stimulate lipid peroxidation and reduce antioxidant defenses in cerebral cortex. Neuroinflammation processes have been also suggested in the etiology of autistic disorder.

Routine metabolic investigation is not recommended in cases with AD. However several metabolic disorders (e.g. phenylketonuria, histidinemia) was found to be associated with autistic symptoms with a rate higher than that found in the general population. Clinicians who diagnose and treat metabolic disorders which are accompanied with mental retardation should be aware of possible diagnosis of ASD.