Bartter and Gitelman syndromes.

Bartter and Gitelman syndromes belong to salt-losing tubulopathies. These rare diseases may be associated with severe electrolyte disorders. Early identification of tubulopathies is essential for appropriate management. Progress in molecular genetics enabled the identification of genes and pathophysiologic mechanisms associated with these diseases. Here, we review etiology and diagnostics of these disorders from the light of current knowledge. Additionally, we discuss contemporary therapeutic approaches.

Complement activation is associated with more severe course of diarrhea-associated hemolytic uremic syndrome, a preliminary study.

Diarrhea-associated hemolytic uremic syndrome is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury secondary to enteric infection, typically Shiga toxin-producing Escherichia coli. Shiga toxin 2 is able to activate alternative complement pathways; therefore, the aim of the study was to analyze C3 as a predictor of clinical courses in patients with diarrhea-associated hemolytic uremic syndrome. We hypothesized that the patients with increased complement activation at admission suffered from a more severe course. We retrospectively analyzed data of 33 pediatric patients between 1999 and 2015 in the Czech Republic. We tested the association of a C3 concentration with biochemical parameters and the clinical data reflecting the severity of the disease. We found significant correlation between the initial C3 and the duration of renal replacement therapy (r = - 0.62, p = 0.0001) and the initial glomerular filtration rate (r = 0.36, p = 0.026). Patients with C3 < 0.825 g/L needed renal replacement therapy and also had significantly more renal complications (p = 0.015).Conclusion: Based on our study, decreased C3 concentrations can be used as one of the risk factors that can help predict the need for acute dialysis and a more severe course of disease in children with diarrhea-associated hemolytic uremic syndrome. What is Known: • Shiga toxin modulates the function of complement regulatory proteins and thus contributes to complement activation in patients with diarrhea-associated hemolytic uremic syndrome. • Risk factors that can predict the need for acute renal replacement therapy and poor outcome in patients with diarrhea-associated hemolytic uremic syndrome are mainly the combination of oligoanuria, dehydration, leukocytosis, high hematocrit > 23%, and neurological involvement. What is New: • A lowered concentration of C3 at the time of initial presentation of diarrhea-associated hemolytic uremic syndrome was associated with more severe renal failure and the need for renal replacement therapy along with the development of more extra renal complications. • Decreased C3 at admission can predict complicated course of diarrhea-associated hemolytic uremic syndrome.

Is Central Europe Safe from Environmental Lead Intoxications? A Case Series.

Preventive measures in Central Europe were successful in suppressing both occupational and environmental lead exposure so that they did not constitute a severe public health problem. However, rare lead intoxications still appear. We report on lead intoxication in four family members where the source was removed lead ceiling paint. The symptoms of the lead intoxication started several weeks after removal and the inhalational exposure to the minimum dust residues lasted for more than three months before the poisoning was diagnosed. Father developed anaemia and saturnine colics. He and his two daughters received antidotal treatment which had to be repeated in the children. Finally, all recovered completely.Lead intoxication may be easily overlooked due to the unspecific symptoms. It is necessary to think of this rare poisoning which may be caused by old paints, historical ceramics and lead shots, in addition to commercial products imported from abroad.

Modern diagnostic approach to hereditary xanthinuria.

Hereditary xanthinuria (HX) is a rare inherited disorder caused by a deficiency of xanthine dehydrogenase/oxidase (XDH/XO). Missing XDH/XO activity leads to undetectable levels of uric acid excessively replaced by xanthine in serum/urine. The allopurinol loading test has been traditionally used to differentiate between HX types I and II. Final confirmation of HX has been based on the biopsy finding of the absent XDH/XO activity in the small intestine or liver. We present the clinical, biochemical, ultrasound and molecular genetics findings in three new patients with HX and suggest a simple three-step approach to be used for diagnosis, typing and confirmation of HX. In the first step, the diagnosis of HX is determined by extremely low serum/urinary uric acid excessively replaced by xanthine. Second, HX is typed using urinary metabolomics. Finally, the results are confirmed by molecular genetics. We advocate for this safe and non-invasive diagnostic algorithm instead of the traditional allopurinol loading test and intestinal or liver biopsy used in the past.

Controlled diet in phenylketonuria and hyperphenylalaninemia may cause serum selenium deficiency in adult patients: the Czech experience.

Phenylketonuria is an inherited disorder of metabolism of the amino acid phenylalanine caused by a deficit of the enzyme phenylalanine hydroxylase. It is treated with a low-protein diet containing a low content of phenylalanine to prevent mental affection of the patient. Because of the restricted intake of high-biologic-value protein, patients with phenylketonuria may have lower than normal serum concentrations of pre-albumin, selenium, zinc and iron. The objective of the present study was to assess the compliance of our phenylketonuric (PKU) and hyperphenylalaninemic (HPA) patients; to determine the concentration of serum pre-albumin, selenium, zinc and iron to discover the potential correlation between the amount of proteins in food and their metabolic control. We studied 174 patients of which 113 were children (age 1-18), 60 with PKU and 53 with HPA and 61 were adults (age 18-42), 51 with PKU and 10 with HPA. We did not prove a statistically significant difference in the concentration of serum pre-albumin, zinc and iron among the respective groups. We proved statistically significant difference in serum selenium concentrations of adult PKU and HPA patients (p = 0.006; Mann-Whitney U test). These results suggest that controlled low-protein diet in phenylketonuria and hyperphenylalaninemia may cause serum selenium deficiency in adult patients.

Intravitreal pegaptanib combined with diode laser therapy for stage 3+ retinopathy of prematurity in zone I and posterior zone II.

PURPOSE: To investigate efficacy of intravitreal injection of pegaptanib and laser photocoagulation for treatment of stage 3+ retinopathy of prematurity (ROP) affecting zone I and posterior zone II, and to compare the results in terms of regression, development of peripheral retinal vessels, and final structural outcome with conventional laser photocoagulation or combined with cryotherapy. METHODS: In a prospective comparative study, 152 eyes with zone I, II posterior ROP 3+ (76 premature rabies), from 2009 to 2011, were included. Patients were randomly assigned to receive intravitreal pegaptanib (Macugen® 0.3 mg = 0.02 mL, Pfizer) with conventional diode laser photocoagulation in group 1 (68 eyes of 34 infants) or only laser therapy combined with cryotherapy in group 2 (84 eyes of 42 infants), bilaterally. The primary outcome of treatment success was defined as absence of recurrence of stage 3+ ROP. The mean follow-up after treatment was 19.3 months in group 1 and 21.5 months in group 2. RESULTS: Final favorable anatomic outcome and stable regression of ROP at last control examination was noted in 89.7% of eyes in group 1 and 60.8 % of eyes in group 2. Regression of plus disease and peripheral retinal vessels development appeared significantly more rapidly in group 1. No recurrence of neovascularization (stage 3+ ROP) was identified in 85.4% of patients in group 1 and 50% of patients in group 2. CONCLUSIONS: Results of this study support the administration of intravitreal pegaptanib as useful therapy in the management of stage 3+ ROP.

Caudal regression syndrome in one of dizygotic twins.

Caudal regression syndrome is a rare congenital condition characterized by varying degrees of developmental failure ranging from a partial sacral agenesis to the absence of lumbosarcal spine, hypoplasia, or fusion of the lower extremities and visceral anomalies. This is the third case of only one of the twins involved by this syndrome described in the literature and the second case of the selective involvement in dizygotic twins. Selective involvement of only one twin suggests that factors other than hyperglycemia and 7q deletions may be involved in the pathogenesis.

Compound heterozygous mutations in the vitamin D receptor in a patient with hereditary 1,25-dihydroxyvitamin D-resistant rickets with alopecia.

Hereditary vitamin D-resistant rickets (HVDRR) is a rare recessive genetic disorder caused by mutations in the vitamin D receptor (VDR). In this study, we examined the VDR in a young girl with clinical features of HVDRR including rickets, hypophosphatemia, and elevated serum 1,25(OH)(2)D. The girl also had total alopecia. Two mutations were found in the VDR gene: a nonsense mutation (R30X) in the DNA-binding domain and a unique 3-bp in-frame deletion in exon 6 that deleted the codon for lysine at amino acid 246 (DeltaK246). The child and her mother were both heterozygous for the 3-bp deletion, whereas the child and her father were both heterozygous for the R30X mutation. Fibroblasts from the patient were unresponsive to 1,25(OH)(2)D(3) as shown by their failure to induce CYP24A1 gene expression, a marker of 1,25(OH)(2)D(3) responsiveness. [(3)H]1,25(OH)(2)D(3) binding and immunoblot analysis showed that the patient's cells expressed the VDRDeltaK246 mutant protein; however, the amount of VDRDeltaK246 mutant protein was significantly reduced compared with wildtype controls. In transactivation assays, the recreated VDRDeltaK246 mutant was unresponsive to 1,25(OH)(2)D(3). The DeltaK246 mutation abolished heterodimerization of the mutant VDR with RXRalpha and binding to the coactivators DRIP205 and SRC-1. However, the DeltaK246 mutation did not affect the interaction of the mutant VDR with the corepressor Hairless (HR). In summary, we describe a patient with compound heterozygous mutations in the VDR that results in HVDRR with alopecia. The R30X mutation truncates the VDR, whereas the DeltaK246 mutation prevents heterodimerization with RXR and disrupts coactivator interactions.

Paroxysmal nocturnal hemoglobinuria in a girl with hemolysis and "hematuria".

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder of unknown frequency. In its classic form, PNH is characterized by hemolysis accompanied by nocturnal hemoglobinuria. The clinical course is unpredictable and may vary from severe hemolysis and recurrent venous thrombosis to latent periods with milder symptoms. We report a 15-year-old girl with hemolytic episodes, abdominal pain, and passage of dark urine. Hemoglobinuria was demonstrated by a "blood"-positive dipstick test in the absence of red blood cells in the urinary sediment. The diagnosis of PNH was confirmed by flow cytometry.