A 3-day-old female infant was brought to the emergency room following an abnormal newborn screening showing markedly increased isovaleryl/2-methylbutyryl carnitine levels (C5; 23.11 μmol/L; reference interval, <0.60 μmol/L) and C5/C2, C5/C0, and C5/C3 ratios. At admission, the patient presented with bradycardia and hypothermia (95.4 °F) and was treated with intravenous fluids. Routine biochemistry testing indicated mild metabolic acidosis (total CO2, 16.6 mmol/L; reference interval, 21–29 mmol/L) and an anion gap of 23 mmol/L. Plasma ammonia was high (168 μmol/L; reference interval, <90 μmol/L) and rose further within a few hours to 445 μmol/L, requiring therapy with sodium phenylacetate/sodium benzoate (Ammonul). No unusual odor was noted from the child or the child's urine. Follow-up plasma acylcarnitine analysis by tandem mass spectrometry confirmed the increased C5 (10.98 μmol/L; reference interval, <0.30 μmol/L). Moreover, to identify the specific defect, a urine sample was sent for organic acid analysis by GC-MS and for acylglycine analysis by liquid chromatography–tandem mass spectrometry. Results of the urine organic acid analysis are shown in Fig. …

Adrenoleukodystrophy (ALD) is caused by pathogenic variants in the ABCD1 gene, encoding for the adrenoleukodystrophy protein (ALDP), leading to defective peroxisomal β-oxidation of very long-chain and branched-chain fatty acids (VLCFA). ALD manifests in both sexes with a spectrum of phenotypes, but approximately 35% of affected males develop childhood cerebral adrenoleukodystrophy (CCALD), which is lethal without hematopoietic stem cell transplant performed before symptoms start. Hence, ALD was added to the Recommended Uniform Screening Panel after the successful implementation in New York State (2013–2016). To date, thirty-five states have implemented newborn screening (NBS) for ALD, and a few programs have reported on the successes and challenges experienced. However, the overall impact of NBS on early detection of ALD has yet to be fully determined. Here, we conducted a retrospective analysis of VLCFA testing performed by our reference laboratory (ARUP Laboratories, Salt Lake City, UT, USA) over 10 years. Rate of detection, age at diagnosis, and male-to-female ratio were evaluated in patients with abnormal results before and after NBS implementation. After NBS inclusion, a significant increase in abnormal results was observed (471/6930, 6.8% vs. 384/11,670, 3.3%; p < 0.0001). Patients with ALDP deficiency identified via NBS were significantly younger (median age: 30 days vs. 21 years; p < 0.0001), and males and females were equally represented. ALD inclusion in NBS programs has increased pre-symptomatic detection of this disease, which is critical in preventing adrenal crisis as well as the severe cerebral form.