AB093. A case of exogenous C5-acylcarnitine giving rise to a false positive result in newborn screening (NBS)

Background and objective: NBS Screening by MS/MS is considered an effective screening test. However, the technique cannot distinguish between isobaric compounds, thus contributing to some false positive results. One such compound is C5-acylcarnitine in the in the identification of isovaleric acidemia (IVA) in the MS/MS profile. To report and contrast the findings of two newborns with C5-acylcarnitine elevations in newborn screening (NBS).

Methods: Blood collected on Guthrie card from newborns between 24-72 hours of life is analyzed by MS/MS. C5-acylcarnitine and its related ratios are measured in DBS sample to identify at risk newborn.

Results: Newborn A: DBS sample C5: 7.96 µmol/L (normal <0.50), C5/C0: 0.99 (normal <0.025), C5/C3: 16.1 (normal <0.40); Plasma acylcarnitines profile: C5: 9.42 µmol/L (normal 0.06-0.29). Urine organic acid profiles showed marked elevations of isovalerylglycine (IVG), ketone bodies and lactate. This profile is consistent with a patient presenting with a diagnosis of IVA. Newborn B: DBS sample C5: 0.84 µmol/L (normal <0.50), C5/C0: 0.041 (normal <0.025), C5/C3: 0.46 (normal <0.40); Despite the abnormal plasma acylcarnitines profile (C5: 4.38 µmol/L, normal 0.06-0.29), the urine acylglycine profile was normal [IVG: 1.02 mg/g Cr (normal 0.3-14.3 mg/g); 2-MBG: 0.16 mg/g Cr (normal: 0.3-7.5 mg/g)]. A 2^nd plasma acylcarnitine showed a lower C5 level (1.49 µmol/L) and a repeat urine organic acid profile was normal; no IVG and 2-MBG detected. Mother’s (Newborn B) plasma acylcarnitines and urine organic acid profiles were normal, ruling out a possible maternal condition. Moreover, it was confirmed that mother and newborn were not on any antibiotics or steroids, which have been previously reported as the causal agents of falsely elevated C5-acylcarnitine. Further investigation revealed mom was using Mustela Nursing Comfort Balm which contained neopentanoate, a compound demonstrated by Boemer et al. [2014] as the causal agent for the false elevation of C5-acylcarnitine in NBS. The elevated C5 levels in the newborn’s plasma samples appear to correspond to the timing of the feed with the blood draw (i.e., the high C5 plasma acylcarnitine result (4.38 µmol/L) corresponds to a blood sample taken within minutes of a feed and the second sample was collected several hours (>2 hours) after the feed (C5: 1.49 µmol/L). Withdrawal of Comfort Balm use eliminated the biochemical derangements in Newborn B and he is clinically well at 10 months.

Conclusions: Neopentanoate in the form of an emollient can cause a C5 false positive result in NBS.

Keywords: Newborn screening (NBS); C5-acylcarnitine; isovaleric academia (IVA)