Evaluation of a commercially available rapid urinary porphobilinogen test

Background: Demonstration of substantially increased urinary excretion of porphobilinogen is the cornerstone of diagnosing acute porphyria crisis. Because porphobilinogen testing is not implemented on clinical chemistry analysers, respective analyses are available in rather few clinical laboratories. The aim of this study was to critically describe and to evaluate a semi-quantitative rapid test for urinary porphobilinogen determination which is commercially available and recommended by the American Porphyria Foundation. Methods: Urinary samples from patients with acute intermittent porphyria and control samples were analysed and the semi-quantitative results were compared with the results obtained by a manual quantitative spectrophotometric method. Results: In all 32 samples studied, acceptable agreement between the results of the rapid test and the quantitative test was observed. Handling of the test was found to be convenient. Conclusions: The assay was found to be reliable and has the potential to increase the availability of porphobilinogen testing in the field

Neurological and Neuropsychological Problems in Tyrosinemia Type I Patients

Clinically, Hereditary Tyrosinemia type I (HTI) is especially characterized by severe liver dysfunction in early life. However, recurrent neurological crises are another main finding in these patients when they are treated with a tyrosine and phenylalanine restricted diet only. This is caused by the accumulation of delta-aminolevulinic acid due to the inhibitory effect of succinylacetone on the enzyme that metabolizes d-aminolevulinic acid. Due to the biochemical and clinical resemblance of these neurological crises and acute intermittent porphyria, this group of symptoms in HTI patients is mostly called porphyria-like-syndrome. The neurological crises in HTI patients disappeared after the introduction of treatment with 2-(2 nitro-4-3 trifluoro-methylbenzoyl)-1,3-cyclohexanedione (NTBC). However, if NTBC treatment is stopped for a while, severe neurological dysfunction will reappear. If NTBC treatment is started early and given continuously, all clinical problems seem to be solved. However, recent research findings indicate that HTI patients have a non-optimal neurocognitive outcome, showing (among others) a lower IQ and impaired executive functioning and social cognition. Unfortunately the exact neuropsychological profile of these HTI patients is not known yet, neither are the exact pathophysiological mechanisms underlying these impairments. It may be hypothesized that the biochemical changes such as high blood tyrosine or low blood phenylalanine concentrations are important in this respect, but an direct toxic effect of NTBC or production of toxic metabolites (that previously characterized the disease before introduction of NTBC) cannot be excluded either. This chapter discusses the neurological and neuropsychological symptoms associated with HTI in detail. An extended section on possible underlying pathophysiological mechanisms of such symptoms is also included