Explore chapters and articles related to this topic
Orotic aciduria
Published in William L. Nyhan, Georg F. Hoffmann, Aida I. Al-Aqeel, Bruce A. Barshop, Atlas of Inherited Metabolic Diseases, 2020
The conceptualization of effective replacement therapy began with the first publication [1]. Administration of uridylic and cytidylic acids led to reduction in orotic acid excretion. This was presumably a consequence of breakdown in the intestine to uridine and cytidine, as oral bioavailability of nucleotides is very low, and their administration usually results in diarrhea. Uridine therapy was initiated by Becroft and Phillips in the second patient [2]. Treatment begun at 16 months with 1.5 g/day led to a prompt rise in hemoglobin and a normal bone marrow. Activity and interest in his surroundings improved immediately, as did appetite. Hair and nails began to grow, as did he, crossing percentile lines for weight from below the 3rd percentile to between the 90th and 97th percentile. He remained mildly mentally impaired, but there was no progression. It was interesting that he experienced a prompt relapse on substitution of uracil for uridine, even though the content of pyrimidine base was twice that of uridine, which at that time was 75 mg/kg. Uridine therapy is dependent for bioavailability on efficient intestinal absorption and the activity of the salvage enzyme uridine kinase (EC2.7.1.48) which leads directly to the formation of the nucleotide UMP [25, 26].
Diagnosis and management of tumor lysis syndrome.
Published in Journal of Community Hospital Internal Medicine Perspectives, 2020
Isha Puri, Deep Sharma, Krishna S. Gunturu, Andaleeb A. Ahmed
A: Allopurinol is the agent of choice in intermediate-risk patients. The usual dose of allopurinol is 100 mg/m2 every 8 h (maximum 800 mg per day) in adults and 50 to 100 mg/m2 every 8 h (maximum 300 mg/m2 per day) or 10 mg/kg per day in divided doses every 8 h in children [6,7]. Dose of allopurinol must be reduced in the setting of acute kidney injury or concomitant administration of azathioprine or mercaptopurine. Intravenous allopurinol must be given in patients who cannot tolerate oral route (dose: 200 to 400 mg/m2 per day, in one to three divided doses (maximum dose 600 mg per day). Xanthine nephropathy and nephrolithiasis is a rare complication of allopurinol therapy especially in patients with deficiencies in the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HGPRT)[10].
Deep brain stimulation for childhood dystonia: current evidence and emerging practice
Published in Expert Review of Neurotherapeutics, 2018
Lior M. Elkaim, Phillippe De Vloo, Suneil K. Kalia, Andres M. Lozano, George M. Ibrahim
LND is a rare, X-linked recessive disorder manifesting in childhood. The disease is caused by mutations in the HPRT1 gene (Xq26-q27.2), which codes for the purine salvage enzyme hypoxanthine-guanine phosphoribosyl transferase (HPRT) [84]. The resulting decrease in HPRT activity is clinically characterized by excessive uric acid production causing gout and lithiasis, global developmental delay, cognitive impairment, and motor anomalies including choreoathetosis, weakness and spasticity mainly in the lower limbs, and severe generalized dystonia [23]. Perhaps the most disabling symptoms are aggression and self-mutilating behavior (SMB) [85], as underlined by the need for drastic interventions including edentulation for compulsive lip and finger biting, physical restraints to avoid self-mutilation, and masks for spitting [86].
Colonic thioguanine pro-drug: Investigation of microbiome and novel host metabolism
Published in Gut Microbes, 2018
Timothy Florin, Ramya Movva, Jakob Begun, John Duley, Iulia Oancea, Páraic Ó. Cuív
In our Gut paper,9 we concluded that colonic microbial metabolism of TG was a significant pathway to deliver TGTP locally to the inflamed gut mucosa. This is the opposite of the usual scenario of drug disposition, where the luminal colonic metabolism is considered to be a metabolic sink that competes with host pro-drug metabolism. This conclusion was supported by the surprising observation that oral TG improved DSS-induced colitis in Hprt (hypoxanthine-guanine phosphoribosyl transferase)-deficient (Hprt-ko) mice. HPRT is the highly conserved purine salvage enzyme. Oral TG was not associated with myelosuppression in Hprt-ko mice. Furthermore, we showed that representative axenic gut bacterial and faecal cultures convert TG to thioguanine nucleotides. Following TG gavage, thioguanine nucleotides were detected in wild type (WT) and Hprt-ko mouse faecal bacteria and in WT liver but not in Hprt-ko mouse liver.