A patient with atypical presentation of chronic hepatosteatosis and developmental delay harboring a novel variant in the CPT1A gene

Abstract Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a rare disorder of hepatic long-chain fatty acid oxidation. Most patients with CPT1A deficiency present with hypoketotic hypoglycemia and hepatic encephalopathy. We present an atypical case of an 8-year-old male with CPT1A deficiency, developmental delay, autistic spectrum disorder and liver cirrhosis. His newborn screening test suggested CPT1A deficiency but confirmatory biochemical testing was not conclusive. The patient never experienced a metabolic crisis. At age six, hepatomegaly was detected. Further investigations showed transaminitis, hepatosteatosis and cirrhosis. Repeat acylcarnitine profile and total/free carnitine were consistent with CPT1A deficiency. The CPTI enzyme activity was 18% of normal on fibroblast enzyme assay. A novel homozygous variant in the CPT1A gene, c.1394G > A (p.G465E), was identified from whole exome sequencing. To our knowledge, the patient is the first reported individual with CPT1A deficiency and chronic liver steatosis and fibrosis. Developmental delay and autistic spectrum disorder are not typical features of CPT1A deficiency given that the patient never experienced any metabolic decompensation.