The (C16+C18:1)/C2 acylcarnitine ratio in dried blood spots is more specific than long-chain acylcarnitine (C16 and C18:1) alone in diagnosing carnitine-acylcarnitine translocase (CACT) and carnitine palmitoyltransferase 2 (CPT 2) deficiencies, according to a new study published in the journal Clinical Biochemistry.

CACT and CPT 2 are 2 types of long-chain fatty acid oxidative disorders (LCFAOD). The diseases can be missed or misdiagnosed if only acylcarnitine levels of the individual were analyzed without looking at their ratio, according to the authors of the study.

The study was conducted to review the clinical, biochemical, and molecular characteristics of the diseases in Malaysian children and led by NguLock-Hockg from the Department of Genetics at Hospital Kuala Lumpur in Malaysia. NguLock-Hockg reviewed the medical records of 6 patients diagnosed with CACT or CPT 2 deficiencies. These patients were identified from a selective high-risk screening of 50,579 patients between January 2010 and June 2020.


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All patients had either high long-chain acylcarnitines and/or a high(C16+C18:1)/C2 acylcarnitine ratio. 

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Two patients had a homozygous splice site mutation at c.199-10T>G in intron 2 of the SLC25A20 gene, which encodes for the CACT enzyme. The researchers identified 2 novel mutations, 1 at c.109C>T p. (Arg37*) in exon 2 and 1 at c.706C>T p. (Arg236*) in exon 7 of the gene in 1 patient.

Another 2 patients, who were siblings, had a compound heterozygous mutation at c.638A>G p. (Asp213Gly) and a novel mutation at c.1073T>G p. (Leu358Arg) in exon 4 of the CPT2 gene.

The researchers calculated a combined prevalence at 0.01% of CACT and CPT 2 deficiencies in symptomatic Malaysian patients.

“CACT and CPT2 deficiencies are rare in Malaysia but appear to be more frequent than [in] other populations,” the authors concluded. “DNA sequencing for both genes aids in confirming the diagnosis.”

Reference

Habib A, Azimah Abdul Azize N, Abd Rahman S, et al. Novel mutations associated with carnitine-acylcarnitine translocase and carnitine palmitoyl transferase 2 deficiencies in Malaysia. Clin Biochem. 2021;6:S0009-9120(21)00273-3. doi:10.1016/j.clinbiochem.2021.10.002