Using the C14:1/Medium-Chain Acylcarnitine Ratio Instead of C14:1 to Reduce False-Positive Results for Very-Long-Chain Acyl-CoA Dehydrogenase Deficiency in Newborn Screening in Japan.

Very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency is a long-chain fatty acid oxidation disorder that manifests as either a severe phenotype associated with cardiomyopathy, a hypoglycemic phenotype, or a myopathic phenotype. As the hypoglycemic phenotype can cause sudden infant death, VLCAD deficiency is included in newborn screening (NBS) panels in many countries. The tetradecenoylcarnitine (C14:1) level in dried blood specimens is commonly used as a primary marker for VLCAD deficiency in NBS panels. Its ratio to acetylcarnitine (C2) and various other acylcarnitines is used as secondary markers. In Japan, tandem mass spectrometry-based NBS, initially launched as a pilot study in 1997, was introduced to the nationwide NBS program in 2013. In the present study, we evaluated levels of acylcarnitine with various chain lengths (C18 to C2), free carnitine, and their ratios in 175 infants who tested positive for VLCAD deficiency with C14:1 and C14:1/C2 ratios. Our analyses indicated that the ratios of C14:1 to medium-chain acylcarnitines (C10, C8, and C6) were the most effective markers in reducing false-positive rates. Their use with appropriate cutoffs is expected to improve NBS performance for VLCAD deficiency.

The perioperative transition of serum biomarkers of a 1.5-year-old boy with very-long-chain acyl-CoA dehydrogenase deficiency.

Very long-chain acyl-coenzyme A dehydrogenase deficiency (VLCADD, OMIM 201475) is a congenital fatty acid oxidation disorder. Individuals with VLCADD should avoid catabolic states, including strenuous exercise and long-term fasting; however, such conditions are required when undergoing surgery. The perioperative management of VLCADD in infants has rarely been reported and details regarding the transition of serum biomarkers reflecting catabolic status have not been disclosed. Herein, we present the perioperative clinical and biological data of cryptorchidism in a 1.5-year-old boy with VLCADD. The patient was diagnosed through newborn screening and his clinical course was very stable. Genetic testing of ACADVL revealed compound heterozygous variants c.506 T > C (p.Met169Thr) and c.606-609delC (p.L216*). The enzyme activity of the patient with VLCAD was only 20% compared to that of healthy control. Left orchiopexy for the pediatric cryptorchidism was planned and performed at 1 and a half year of age. Induction anesthesia involved thiopental, fentanyl and rocuronium. The glucose infusion rate was maintained above 6.6 mg/kg/min starting the day before surgery until the operation was completed. Anesthesia was maintained with sevoflurane at approximately 2%. The serum concentration of tetradecenoylcarnitine were stable during the operation, ranging between 0.08 and 0.19 µM (cutoff <0.2 µM), and never deviated from the reference range. Concentration of other serum biomarkers including free fatty acid, 3-OH-butyrate, and creatine kinase, remained similarly unchanged. In this report, we describe the uneventful perioperative management of unilateral orchiopexy for left cryptorchidism in a 1.5-year-old boy with VLCADD using sufficient glucose infusion and volatile anesthesia.