ABSTRACT
We report on a girl who was diagnosed with classical hereditary xanthinuria due to an incidental finding of extremely low Levels of uric acid in the blood. The girl is compLetely asymptomatic. Hereditary xanthinuria is a rare autosomal recessive disease that usually causes early urolithiasis but may cause rheumatoid arthritis-like disease and even be associated with defects in the formation of bone, hair and teeth. In Israel it has mostly been described in patients of Bedouin origin. Throughout the world, only about 150 cases have been described; about two thirds of these patients were asymptomatic. Since the clinical presentation and age of symptom appearance are diverse, the case raises questions as to the required follow-up of these patients and as to whether a low oxalate diet should be initiated.
Subject(s)
Diet Therapy/methods , Purine-Pyrimidine Metabolism, Inborn Errors , Watchful Waiting/methods , Xanthine , Arabs , Asymptomatic Diseases , Child, Preschool , Disease Management , Female , Humans , Incidental Findings , Israel/epidemiology , Monitoring, Physiologic/methods , Oxalates/metabolism , Purine-Pyrimidine Metabolism, Inborn Errors/complications , Purine-Pyrimidine Metabolism, Inborn Errors/ethnology , Purine-Pyrimidine Metabolism, Inborn Errors/metabolism , Purine-Pyrimidine Metabolism, Inborn Errors/physiopathology , Purine-Pyrimidine Metabolism, Inborn Errors/therapy , Treatment Outcome , Uric Acid/blood , Uric Acid/urine , Xanthine/metabolism , Xanthine/urineABSTRACT
A condition called thymine uracilurea has been described that is due to a lack of dihydropyrimidine dehydrogenase (DPD) activity. Cancer patients experiencing acute 5-fluorouracil toxicity also have lower-than-normal DPD activities. However, to date, the molecular basis of this disorder has not been addressed. In this study, the phenotype and genotype of a family that presents a patient showing no DPD activity was determined. Fibroblast mRNAs from the patient and four family members were subjected to reverse transcriptase polymerase chain reaction (RT-PCR) using primers generated from the human DPD cDNA sequence. DPD mRNA from the patient was found to lack a segment of 165 nucleotides that results from exon skipping. DPD mRNA from the parents and a sibling were found to be heterozygous for the deleted and the normal mRNA, while a brother had two normal transcripts. DPD activities and levels of DPD protein correlated with genotype; the deficient patient had no detectable DPD protein. PCR analysis of the genomic DNA from this family revealed that the defective mRNA is not due to a deletion of a portion of the gene that contains the exon, thus implying that the mutation is the result of an as yet nonidentified point mutation that causes faulty splicing.
