Nitisinone (2-[2-nitro-4-trifluoromethylbenzoyl]cyclohexane-1,3-dione), an effective triketone herbicide, is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, the second enzyme in the tyrosine catabolic pathway. Since 1992, the drug has become an effective pharmacological treatment for hereditary tyrosinemia type 1 (HT1). Nitisinone can prevent the development of liver disease, reverse and prevent the renal tubular dysfunction, severe neurological crisis and cardiomyopathy and significantly reduce the risk of developing hepatocellular carcinoma in HT1 patients. Its mode of action, with few side effects reported, make the drug a potential candidate for the treatment of other disorders of tyrosine metabolism, including alkaptonuria, with successful reduction in homogentisic acid production to prevent long-term complications. Nitisinone could also be a promising agent in the treatment of tumors with active tyrosine metabolic pathways. In this review, we discuss the effects of nitisinone for various tyrosine pathway disorders.

While Continuous Renal Replacement Therapy (CRRT) is a well established treatment modality for patients with acute kidney insufficiency (AKI), it is now also being used for the management of various illnesses such as acute metabolic disorders presenting with hyperammonemia and elevated leucine levels. Herein, we aimed to describe our experience with CRRT in treatment of acute decompensation of 14 patients with a diagnosis of metabolic disorder who has been admitted to our pediatric intensive care unit (PICU) in the last year. Patients who have had life threatening acute metabolic crisis due to various metabolic disorders and were treated with continuous renal replacement therapy (CRRT) were evaluated retrospectively. Between November 2014 and December 2015, 14 patients were found to have received CRRT for various metabolic disorders in the PICU. Ten patients had hyperammonemia and four patients had elevated leucine levels. Nine patients were male and five were female. The age interval was between 2 days and 18 months, with a mean of 5.5 ± 7.4 months. The weight distribution was between 2.5 and 18 kg, with a mean of 7.3 ± 5.6 kg. Eleven patients received continuous veno-venous hemodiafiltration (CVVHDF), and 3 patients with MSUD received continuous veno-venous hemodialysis (CVVHD). All patients have received high throughput hemodialysis and hemofiltration. The dialyzate rate was set to be minimum 4042 ml/h/1.73 m2, and maximum 12,900 ml/h/1.73 m2. Hemofiltration was performed with a replacement rate of 40-76 ml/kg/h. The average CRRT duration was 16.6 ± 15.6 h. We suggest that CRRT is an efficient method that can be used in hyperammonemia and elevated leucine levels which are metabolic emergencies.

Cite this article as: Aktuğlu Zeybek AÇ. Newborn screening: From the past to the future. Turk Arch Pediatr. 2022;57(5):473-475.