Adenine phosphoribosyltransferase deficiency in the United Kingdom: two novel mutations and a cross-sectional survey.

BACKGROUND: Adenine phosphoribosyltransferase deficiency is an inborn error of metabolism that can cause kidney disease from crystalline nephropathy or kidney stones. METHODS: We present three cases from a single centre with varied presentations to illustrate how increasing awareness led to better patient identification. We then undertook a cross-sectional survey of all the patients identified from the Purine Research Laboratory in the UK since 1974. RESULTS: Our index case presented with recurrent nephrolithiasis and was diagnosed on stone analysis, the second case presented with acute kidney injury and the third case was identified from a biopsy undertaken for acute on chronic kidney injury. Genetic studies identified two novel mutations. Twenty patients were retrospectively identified. The mean age at diagnosis was 25 years (range 2-70); eight were <20 years, seven were 20-40 years and five were >40 years. Five of the 20 patients were deceased, 3 after end-stage renal disease (ESRD). Twelve have normal renal function, one had CKD stage 3, one had severe kidney disease and one was on dialysis. CONCLUSIONS: Adenine phosphoribosyltransferase deficiency presents in a wide spectrum in all age groups. Patients can be completely asymptomatic and kidney disease may be incorrectly attributed to other conditions. Outcome is poor in late diagnosis and there is a high prevalence of ESRD. Patients with unexplained renal stone disease or deterioration in kidney function should be considered for screening. Identification and surveillance of patients in the UK can improve. There is now a rare disease registry with meetings organized that include patients, families and health care providers to improve awareness.

A Multipronged Comparative Study of the Ultraviolet Photochemistry of 2-, 3-, and 4-Chlorophenol in the Gas Phase.

The S1((1)ππ*) state of the (dominant) syn-conformer of 2-chlorophenol (2-ClPhOH) in the gas phase has a subpicosecond lifetime, whereas the corresponding S1 states of 3- and 4-ClPhOH have lifetimes that are, respectively, ∼2 and ∼3-orders of magnitude longer. A range of experimental techniques-electronic spectroscopy, ultrafast time-resolved photoion and photoelectron spectroscopies, H Rydberg atom photofragment translational spectroscopy, velocity map imaging, and time-resolved Fourier transform infrared emission spectroscopy-as well as electronic structure calculations (of key regions of the multidimensional ground (S0) state potential energy surface (PES) and selected cuts through the first few excited singlet PESs) have been used in the quest to explain these striking differences in excited state lifetime. The intramolecular O-H···Cl hydrogen bond specific to syn-2-ClPhOH is key. It encourages partial charge transfer and preferential stabilization of the diabatic (1)πσ* potential (relative to that of the (1)ππ* state) upon stretching the C-Cl bond, with the result that initial C-Cl bond extension on the adiabatic S1 PES offers an essentially barrierless internal conversion pathway via regions of conical intersection with the S0 PES. Intramolecular hydrogen bonding is thus seen to facilitate the type of heterolytic dissociation more typically encountered in solution studies.

Allosensitization rate of male patients awaiting first kidney grafts after leuko-depleted blood transfusion.

BACKGROUND: Blood transfusions are generally avoided for potential renal transplant recipients due to risk of human leukocyte antigen (HLA) allosensitization. Despite the near universal use of erythropoiesis-stimulating agents, there are still occasions when patients require blood transfusions for reasons such as resistance to erythropoiesis-stimulating agents or cardiovascular instability. The risk of allosensitization in renal patients is believed to be lower with leuko-depleted blood. We sought to quantify the risk of blood transfusion per se in male renal patients on the transplant waiting list for their first kidney graft, using sensitive solid phase antibody detection. METHOD: Cross-sectional survey looking at the prevalence of HLA antibody detected using single antigen Luminex beads in male patients awaiting first renal transplantation. RESULTS: One hundred sixteen male patients awaiting their first kidney transplant were identified on our waiting list. Seven of the 42 patients (16.7%) who received at least one unit of leuko-depleted blood developed HLA antibody (HLAab). Of the remaining 74 patients without a history of transfusion, 3 (4.1%) were found to have HLAab. All the antibodies identified were directed against class I antigens. A history of blood transfusion gave a relative risk of 4.1 of developing HLAab (P=0.02). CONCLUSION: Male patients awaiting their first organ transplant had a fourfold increased risk of developing HLA antibody if they had been previously transfused when compared with those who did not have a history of a transfusion. Transfusion even in the postleukodepletion era continues to pose a significant risk of sensitization.