Genetic Testing Important for Symptomatic LCFAOD Patients of All Ages

Adolescents and adults with very long-chain acyl-coenzyme A dehydrogenase (VLCAD) and carnitine palmitoyltransferase II (CPT II) deficiencies report clinical signs that overlap with neuromuscular disorders. Next-generation sequencing analysis using a panel of 35 genes associated with long-chain fatty acid oxidation disorder (LCFAOD) or other conditions that cause abnormal plasma acylcarnitine profiles allowed the identification of these patients as having LCFAOD.

This is according to an abstract published in a special issue of Neuromuscular Disorders, the official journal of the World Muscle Society (WMS), which included abstracts from the WMS’s 26th International Annual Congress that took place September 20-24, 2021.

The authors of the study, which reported data for adolescents and adults aged 13 years and older, wrote, “Our findings highlight the value of genetic testing for symptomatic patients of all ages.”

Two types of LCFAOD—VLCAD and CPT II deficiencies—may present late, and the symptoms may overlap with those of neuromuscular diseases.

Read more about LCFAOD differential diagnosis

Here, the researchers used data from 205 patients who were tested for LCFAOD as part of a no-charge genetic test through a sponsored program available to people with a clinical diagnosis or suspicion of LCFAOD.

Fifty-five (27%) patients were adolescents or adults aged 13 to 92 years. Of these, 35 (65.4%) reported 1 or more clinical sign, including muscle myopathy, elevated creatine kinase, rhabdomyolysis, hypoketotic hypoglycemia, and myoglobinuria.

Of all patients who were tested, 22 (11%) had a positive or potential positive molecular diagnosis in a gene associated with LCFAOD. Four of them were adolescents or adults. One 42-year-old patient had elevated creatine kinase, muscle myopathy, and rhabdomyolysis, as well as a mutation in the CPT2 gene. The other 3 had a mutation in the ACADVL gene, which causes VLCAD deficiency. A 36-year-old patient had exercise intolerance. A 19-year-old patient had elevated creatine kinase and transaminases, as well as rhabdomyolysis and reported VLCAD deficiency. Finally, the last person, aged 17 years, had no reported clinical history.

Reference

Marsden D, Rangel Miller V, Chettiath T, et al. EP.207 Clinical findings of late-onset long-chain fatty acid oxidation disorders overlap with neuromuscular conditions in a sponsored genetic testing program. Neuromuscul Disord. 2021;31(1);S112. doi:10.1016/j.nmd.2021.07.232