Inborn errors of purine and pyrimidine metabolism

Abstract

Genetic disorders of purine and pyrimidine (PP) metabolism are under-reported and infrequently mentioned in the general literature, as well as in reviews dedicated to other inborn errors of metabolism. Owing to limited awareness, relatively recent recognition, as well as considerable phenotypic variation, these disorders may often be misdiagnosed or remain undiagnosed. Disorders that arise as a result of dysfunction in PP metabolism represent some of the most challenging diagnostic problems in medicine. In addition to their low prevalence rates, they also present with extremely variable signs and symptoms. They may affect any system in a variety of manners, and often mimic other, more recognizable disorders. The diagnostic problem is compounded by the fact that some biochemically affected patients are symptom-free. Rapidly evolving laboratory techniques such as high-performance liquid chromatography coupled to tandem mass spectrometry are now well established as the preferred method for detection for these defects, but currently the most important step in diagnosis consists of suspecting the disorder. Diagnosis is vital because genetic counselling can be provided and, in some cases, specific treatment can be offered that may slow or even reverse clinical symptoms. If undiagnosed, these disorders can be devastating to patients and their families, resulting in early death or institutionalization for the rest of patient's life. This article describes the current state of knowledge about inborn errors of purine and pyrimidine metabolism, focusing on the varying clinical presentations, the laboratory findings and discusses indications for selective screening for these disorders.

Dihydropyrimidinase Deficiency: The First Feline Case of Dihydropyrimidinuria with Clinical and Molecular Findings

“…The GC-MS analysis demonstrated gross elevations in dihydrouracil and dihydrothymine, that is, DHPuria, as well as moderate elevations in uracil and thymine. These findings strongly suggested that the cat was affected with a DHP deficiency, one of the inborn errors of pyrimidine metabolism, according to the typical GC-MS spectrum in human urine from DHP-deficient patients (Jurecka 2009). In the cat with DHPuria, activity of DHP has not been measured using liver and/or kidney, the only specimens available for enzymatic confirmation (Assmann et al 1997;Van Gennip et al 1997), because of the risk posed by a general anesthesia and difficulty in the measurement of DHP activity.…”

Novel two-step derivation method for the synchronous analysis of inherited metabolic disorders using urine

“…So far, we have examined only 3 cases with thymine-uracil aciduria combined with β-ureidopropionase deficiency (c.C216C/T and c.G977G/A), two cases with thymine-uracil aciduria (c.C216C/T), two cases with β-ureidopropionase deficiency (c.C792C/A combined c.G977G/A), and two cases with orotic aciduria to be examined. However, the prevalence of these metabolic disorders in Europe is reportedly only 26/3.2 million (46)(47)(48), suggesting that conventional methods by urine could have been affected in the course of investigation and thus lead to a false negative or incorrect result, which requires further investigation. Therefore, urine samples were pretreated at room temperature, and fine pH-value variation was required to obtain the optimal conditions.…”

Renal manifestations of rheumatic diseases. A review

“…Uric acid stones are more often found in hereditary hyperuricemic syndromes (Lesch-Nyhan syndrome, HPRT deficiency, PRPS hyperactivity, glycogenosis type I/glycogen storage disease type I) (ref. 42 ).…”