Iminoglycinuria is an autosomal recessive disorder of renal tubular transport affecting reabsorption of the amino acid glycine, and the imino acids proline and hydroxyproline. This results in excess urinary excretion of all three acids (-uria denotes "in the urine").Iminoglycinuria is a rare and complex disorder, associated with a number of genetic mutations that cause defects in both renal and intestinal transport systems of glycine and imino acids.Imino acids typically contain an imine functional group, instead of the amino group found in amino acids. Proline is considered and usually referred to as an amino acid, but unlike others, it has a secondary amine. This feature, unique to proline, identifies proline also as an imino acid. Hydroxyproline is another imino acid, made from the naturally occurring hydroxylation of proline. Presentation
The primary characteristic of iminoglycinuria is the presence of glycine and imino acids in the urine. Otherwise, it is thought to be a relatively benign disorder, although symptoms associated with disruptions of proline and glycine metabolism caused by malabsorption may be present with iminoglycinuria. These include encephalopathy, mental retardation, deafness, blindness, kidney stones, hypertension and gyrate atrophy.Gyrate atrophy is an inherited degenerative disorder of the retina and choroid, sometimes accompanying the metabolic condition hyperornithinemia. The presence of gyrate atrophy with iminoglycinuria stems from a deficiency of proline in chorioretinal tissues, while processes behind hyperornithinemia disrupt the metabolic pathway from ornithine to proline, which alters the catabolism of ornithine, and also results in reduced levels of proline.
Pretomanid is an antibiotic medication used for the treatment of multi-drug-resistant tuberculosis affecting the lungs. It is generally used together with bedaquiline and linezolid. It is taken by mouth.The most common side effects include nerve damage, acne, vomiting, headache, low blood sugar, diarrhea, and liver inflammation. It is in the nitroimidazole class of medications.Pretomanid was approved for medical use in the United States in August 2019, and in the European Union in July 2020. Pretomanid was developed by TB Alliance. The U.S. Food and Drug Administration (FDA) considers it to be a first-in-class medication. Medical uses
Pretomanid is indicated in combination with bedaquiline and linezolid, in adults, for the treatment of pulmonary extensively drug resistant (XDR), or treatment-intolerant or nonresponsive multidrug-resistant (MDR) tuberculosis (TB). History
Pretomanid is the generic, nonproprietary name for the novel anti-bacterial drug compound formerly called PA-824. Pretomanid is referred to as "Pa" in regimen abbreviations, such as BPaL. The "preto" part of the compounds name honors Pretoria, South Africa, the home of a TB Alliance clinical development office where much of the drugs development took place, while the "-manid" stem designates compounds with similar chemical structures. This class of drug is variously referred to as nitroimidazoles or nitroimidazooxazines. Development of this compound was initiated because of the urgent need for new antibacterial drugs effective against resistant strains of tuberculosis. Also, current anti-TB drugs are mainly effective against replicating and metabolically active bacteria, creating a need for drugs effective against persisting or latent bacterial infections as often occur in patients with tuberculosis.