According to a case series in Turkey, genetic metabolic diseases such as Sanfilippo syndrome can underlie a diagnosis of autism spectrum disorder (ASD), especially if they are accompanied by additional symptoms.
The data suggest that 3.3% of ASD cases may have a metabolic genetic cause, which in many cases can be mitigated or corrected with appropriate treatment.
It is therefore crucial that doctors carefully and carefully analyze the additional signs and symptoms of ASD patients, as well as their family history, in order to be able to decide whether to test for metabolic disorders, the researchers noted.
The study, “Cases of Congenital Metabolic Disorders diagnosed in children with autism, ”Was published in the journal Clinical Neuroscience.
ASD is a neurodevelopmental disorder characterized by impaired social interaction and communication, and repetitive or restrictive behaviors. It is estimated that one in 160 children worldwide and one in 54 in the US have ASD.
The underlying cause remains uncertain, but research suggests that it results from a complex combination of genetic, molecular, and environmental factors. Over the past decade, more and more studies have shown a link between genetic disorders – including those that cause metabolic disorders – and ASD.
Sanfilippo syndrome, also called mucopolysaccharidosis (MPS) type III, is one such genetic metabolic disorder that can lead to ASD symptoms.
In particular, a previous review study found that the ASD profile in Sanfilippo patients consists of communication and social difficulties with little evidence of repetitive or restricted behavior. It has also been suggested that doctors should consider screening for Sanfilippo syndrome if their patients have symptoms of ASD, along with other physical and developmental problems.
Now researchers at the University of Health Sciences in Turkey set out to analyze the frequency and type of genetic metabolism disorders in children and adolescents diagnosed with ASD, followed by a single center.
They retrospectively analyzed the demographic, clinical, and laboratory data of 179 ASD patients with no evidence of other underlying genetic / neurological diseases who applied to their pediatric metabolism outpatient clinic between September 2018 and February 2020.
Based on specific blood and urine metabolism examinations, six (3.3%) ASD patients between the ages of 5.5 and 17 years were diagnosed with a disorder of the genetic metabolism.
Two adolescent boys had classic phenylketonuria (PKU), two other boys had classic homocystinuria (HCU), one girl had Sanfilippo syndrome type D, and one boy had 3-methylcrotonyl-Co-A carboxylase deficiency (3- MCC).
In particular, the seven-year-old girl with Sanfilippo showed learning difficulties, hyperactivity, and rough facial features – which led to metabolic tests. Another evaluation found no eye or heart problems, but the presence of skeletal abnormalities suggested MPS.
Enzymatic tests showed that the girl who was diagnosed with ASD 3.5 years earlier was deficient in N-acetylglucosamine-6-sulfatase enzyme, confirming a diagnosis of Sanfilippo type D. In the absence of targeted therapies for the disease, she has been given supportive care for her symptoms.
Notably, four cases, including the girl with Sanfilippo, were born to consanguineous (blood-related) parents, a factor known to increase the risk of genetic metabolic diseases.
For most of these conditions, a child must inherit two mutated copies of a particular gene (one from the mother and one from the father) in order to develop the disease – a more likely situation when the parents have similar genetic backgrounds. The consanguineous marriage rate in Turkey is very high, the team found.
Symptoms in three boys – one with PKU, one with HCU, and one with 3-MCC – subsided after appropriate treatment. In addition, family screening made it possible to diagnose genetic metabolic disorders in two relatives, one of whom showed a reduction in symptoms after specific treatment.
“Careful review of the medical history, physical exam, and additional findings in patients diagnosed with Autism Spectrum Disorder will help the clinician make a decision [in choosing] the corresponding specific metabolic study, ”the researchers wrote.
In particular, “an underlying congenital metabolic abnormality may be a treatable cause of autism,” the team wrote.
Among the limitations of the study, the researchers found that the metabolic tests performed did not cover all metabolic disorders, meaning that some may have been missed in these pediatric patients with ASD. Genetic testing was also not performed in cases where genetic metabolic disorders were diagnosed.