Autism has long existed, but has only been clearly characterized in the last few decades or so. We now recognize it as a spectrum, meaning that diagnosis of this condition is not always a straightforward yes or no. This is in line with modern psychological understanding about human development and growth. 

In an unfortunate coincidence, our understanding of autism rose at the same time that childhood vaccination programs were being heavily advocated by doctors. The resulting collision was a false claim made by a British doctor that continues to haunt medicine today: that a link exists between the measles, mumps, and rubella (MMR) vaccine and autism. 

The antivaccine movement gained steam, and soon enough public opinion regarding childhood vaccinations became sharply divided. Understandably, the medical community has developed a special sensitivity when discussing possible causes or associations with autism, lest it gives further ammunition to individuals who believe that modern medicine is insidiously contributing to the rise of autism. 


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However, we should not shy away from legitimate debate about risk factors for autism just because misinformation in this area is widespread. In Advances in Neurology and Neuroscience, Guevara-Campos and colleagues proposed that primary carnitine deficiency, a type of long chain fatty acid oxidation disorder, is a risk factor for the development of autism spectrum disorder. 

Three Possible Connections 

Patients with autism demonstrate a decreased ability to communicate and interact socially. In addition, they have characteristic behavior patterns and interests. A cause for autism spectrum disorders has not been conclusively identified. 

“Growing evidence suggests that autism is a multifactorial disease influenced by genetic and environmental factors. [Autism spectrum disorder] is associated with several genetic disorders and several studies have uncovered a range of metabolic abnormalities associated with non-syndrome cases of [autism spectrum disorder],” Guevara-Campos et al wrote. “One of these is the alterations of carnitine and its derivatives.” 

The primary function of carnitine is to transport long chain fatty acids to the mitochondria for B oxidation. Hence, carnitine allows fatty acids to participate in the process of energy release; if fatty acids were unavailable, glucose would become the default energy source, and the resulting consumption of glucose may result in hypoglycemia. 

Read more about long chain fatty acid oxidation disorder etiology 

So how do we get from carnitine deficiency to autism? There are 3 possible links. The first is that studies have uncovered alterations of mitochondrial function in patients with autism spectrum disorder. Since primary carnitine deficiency directly alters mitochondrial function, some scientists have proposed a link between the disorders. 

Second, studies have elucidated how L-carnitine levels are somehow associated with severity of autism. Medical literature indicates that patients with autism spectrum disorder have almost a 50% decrease in L-carnitine levels compared to other children. 

“This defect in L-carnitine levels is associated with mitochondrial dysfunction,” Guevara-Campos and colleagues wrote. “Carnitine binds acyl residues and helps in their elimination.” 

Third, a defect in the transport of L-carnitine into the cells impairs fatty acid oxidation, which can give rise to acute metabolic decompensation in early childhood. Children become more irritable, lethargic, and refuse to eat. If left untreated, they may progress to coma and death. 

Read more about long chain fatty acid oxidation treatment 

The theory here is that metabolic dysregulation results in children missing the golden opportunity to learn appropriate communication and socializing skills during the first years of life. Some scientists believe carnitine also plays a role during critical periods of brain development. 

An Illustrative Case Study 

In Brain Sciences, Guevara-Campos and colleagues presented the case report of a female child with a few comorbidities, including primary carnitine deficiency and autism. 

The 7-year-old girl presented with frequent bouts of sweating, vomiting, fatigue, low glucose levels, and generalized muscle weakness from an age of 3 years. She also presented with growth and language delay and was referred to a pediatric neurologist. 

When the child was 12 months old, she said her first raw words. Her language skills were considered poor for her age, and she was diagnosed with moderate intellectual disability. 

“The final diagnosis was moderated [intellectual disability] and a pervasive developmental disorder not otherwise specified (according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-V) criteria and the Autism Diagnostic Interview — Revised,” Guevara-Campos and colleagues wrote. 

Laboratory tests revealed that she had very low levels of plasma free carnitine levels (4.3 μM; normal range: 25-50 μM). Her blood plasma acylcarnitine panel results returned normal, except for 3-OH-iso-butyrylcarnitine (0.13 μM; normal range <0.5 μM). 

Her physicians ordered a molecular genetic test; it demonstrated a heterozygous pathogenic variant, c.1345T>G (p.Y449D, p.Tyr449Asp) in the SLC22A5 gene located in exon 8. This missense variant is commonly observed in patients with primary carnitine deficiency. 

The patient was started on L-carnitine and vitamin B complex. Currently, at age 9, the child attends a special school, and her language skills have improved. However, she still remains inattentive in class. 

“She still has autistic features, although her [intellectual disability] has improved by 15 IQ points relative to her cognitive function before the [primary carnitine deficiency] diagnosis and carnitine treatment,” the authors of the study reported. 

The main takeaway of this study is that carnitine deficiency should be dealt with adequately due to its possible association with autism spectrum disorder. It may also be helpful for physicians to consider patients with primary carnitine deficiency as being at risk of developing autism.

References

Guevara-Campos J, González-Guevara L, Guevara-González J, Cauli O. First case report of primary carnitine deficiency manifested as intellectual disability and autism spectrum disorderBrain Sci. 2019;9(6):137. doi:10.3390/brainsci9060137

Guevara-Campos J, Guevara J, Rojas F. Primary carnitine deficiency and autism spectrum disorder — is there a relationship? Neurol Clin Neurosci. Published August 12, 2021.