Marker ratios could better identify the presence of a long-chain fatty acid oxidation disorder (LCFAOD) than the values of 1 or more markers alone, according to a study recently published in Translational Pediatrics.

“If the ratios were added to the diagnostic indices in addition to long-chain acylcarnitines, [carnitine-acylcarnitine translocase (CACT)] deficiency could be diagnosed based on [tandem mass spectrometry (MS/MS)] data for the 15 patients,” the authors wrote.

This observational study included 28,329 patients from the MS/MS data who underwent newborn screening. Most of them (99.75%) had a negative result for LCFAOD, 53 obtained a false-positive result, and only 15 were true positives. All patients with LCFAOD had CACT deficiency, came from 14 different unrelated families, and presented with respiratory and cardiac arrest.

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A positive result followed the inclusion of at least 3 positive primary acylcarnitine markers, such as C14, C16, C16:1, C18, C18:1, and C18:2. All patients with false-positive results underwent genetic testing to rule out the presence of LCFAOD.

The researchers classified participants with CACT deficiency into 3 groups according to their biochemical profile: the first group included 7 patients who had a classic presentation, the second group included 2 participants who had significantly lower C0 levels while maintaining a normal long-chain acylcarnitine concentration, and the third group included 7 individuals who had interfering acylcarnitines. The authors noted that patients in the second and third groups were subject to misdiagnosis.

The study suggests that basing the diagnosis on marker ratios instead of values could yield more accurate results. All 15 cases of LCFAOD had increased values in 16 different ratios, including C14/C3, C16/C2, C16/C3, C16:1/C3, C16:1-OH/C3, and C18/C3.

Moreover, all ratios were consistently lower in the 18,261 healthy patients except for (C16 + C18)/C0, which showed even lower values than acylcarnitine indices.

“None of the single long-chain acylcarnitines could separate patients from the false-positive cases; however, all ratios produced good discrimination between the two groups,” the authors concluded.


Shi C, Ao Z, Liu B, et al. Increased acylcarnitine ratio indices in newborn screening for carnitine-acylcarnitine translocase deficiency shows increased sensitivity and reduced false-positivity. Transl Pediatr. Published online May 30, 2023. doi:10.21037/tp-22-468