The case of an infantile-onset carnitine palmitoyltransferase 2 (CPT II)-deficient patient with cerebral malformations detected during his adolescent years was reported by Shelihan et al. To the best of their knowledge, the case recently published in JIMD Reports is the first of its kind to be described.

CPT II deficiency is a type of long chain fatty acid oxidation disorder (LCFAOD) caused by mutations in the CPT2 gene. This genetic alteration impairs the carnitine shuttle and prevents the catabolism of long chain fatty acids.

At the age of 5 months, the patient presented clinically with dehydration and hepatomegaly. During diagnostic investigations, all CPT2 exons and surrounding intronic regions were sequenced. The patient revealed compound heterozygosity for 2 pathogenic variants, c.887G>A (p.Arg296Gln, paternal origin) and c.1891C>T (p.Arg631Cys, maternal origin).

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He had also been diagnosed with X-linked nephrogenic diabetes insipidus and recurrent rhabdomyolysis. His psychomotor abilities developed normally for his age.

The patient developed 2 episodes of spontaneous focal seizures at the age of 17 years. Findings on cerebral magnetic resonance imaging (MRI) revealed cerebral malformations.

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“Remarkably, the patient remained neurologically asymptomatic for 17 years despite having a large and complex malformation including extensive polymicrogyria, closed lip schizencephaly, subcortical grey matter heterotopias, and hippocampal dysplasia,” the authors said. “The normal psychomotor development of our patient despite his extensive brain malformations, suggests that the involved regions retained considerable functional capacity.”

The authors performed a comprehensive literature review to analyze the occurrence of brain malformations in CPT II-deficient patients. They found that brain malformations occurred in 61.5% of the neonatal-onset CPT II-deficient patients who met the inclusion criteria (n=26). However, out of the 19 infantile-onset cases that did not report brain malformations, only 3 included brain imaging or neuropathology data. In addition, no brain malformations were reported in adult-onset cases (n=276).

According to the authors’ experience, they believe that cerebral malformations and consequent brain imaging should be considered in any CPT II-deficient patient with unexplained neurological manifestations, regardless of the age of clinical onset.


Shelihan I, Rossignol E, Décarie J-C, et al. Infantile onset carnitine palmitoyltransferase 2 deficiency: cortical polymicrogyria, schizencephaly, and gray matter heterotopias in an adolescent with normal development. JIMD Rep. Published online September 29, 2021. doi:10.1002/jmd2.12243