In this case report and literature review, we report a novel mutation in the ACSL4 gene leading to X-linked intellectual disability (XLID), autism spectrum disorder (ASD), and attention-deficit/hyperactivity disorder (ADHD) 

Intellectual disability (ID) has prevalence of 1-3% with a male predominance. Isolated cases of ACSL4-associated XLID are rare in the literature. ACSL4(Xq22.3-q23) encodes FACL4 (long-chain-fatty-acid—CoA ligase 4), an enzyme that is part of the long-chain fatty acid coenzyme A ligase family. FACL4 is expressed in various tissues, including the brain and liver, and functions in lipid metabolism, signal transduction, and apoptosis

A 5-year old boy presented with intellectual disability as well as symptoms consistent with both an ASD and ADHD.  Initial genetic work-up included Fragile X gene repeat testing, chromosome karyotype, and comparative genomic hybridization (CGH) microarray, all of which were normal.  Next Generation Sequencing on 454 genes associated with diseases which are inherited in an autosomal recessive pattern (Inherited Recessive Disease Panel) was then sent. Sequencing reveled a possibly pathogenic hemizygous frameshift mutation in the ACSL4 gene: NP_075266.1:p.Ala490HisfsTer10.  Sanger sequencing was then performed in the patient and his sister, mother and father.  Sanger sequencing revealed that the patient’s mother and sister were carriers of the same ACSL4 mutation, while his father did not carry the mutation. Mother had mild symptoms of inattention in school whereas the sister fulfilled criteria for ADHD-predominantly hyperactive/impulsive type.  Both the mother and sister were of normal intelligence