Mitochondrialneurogastrointestinalencephalomyopathy (MNGIE) is an autosomal recessive human disease due to mutations in the thymidine phosphorylase (TP) gene. TP enzyme catalyzes the reversible ...phosphorolysis of thymidine to thymine and 2-deoxy-d-ribose 1-phosphate. We present evidence that thymidine metabolism is altered in MNGIE. TP activities in buffy coats were reduced drastically in all 27 MNGIE patients compared with 19 controls. All MNGIE patients had much higher plasma levels of thymidine than normal individuals and asymptomatic TP mutation carriers. In two patients, the renal clearance of thymidine was ∼20% that of creatinine, and because hemodialysis demonstrated that thymidine is ultrafiltratable, most of the filtered thymidine is likely to be reabsorbed by the kidney. In vitro, fibroblasts from controls catabolized thymidine in medium; by contrast, MNGIE fibroblasts released thymidine. In MNGIE, severe impairment of TP enzyme activity leads to increased plasma thymidine. In patients who are suspected of having MNGIE, determination of TP activity in buffy coats and thymidine levels in plasma are diagnostic. We hypothesize that excess thymidine alters mitochondrial nucleoside and nucleotide pools leading to impaired mitochondrial DNA replication, repair, or both. Therapies to reduce thymidine levels may be beneficial to MNGIE patients.
Background Little information on the management and long-term follow-up of patients with biallelic mutations in the chloride channel gene CLCNKB is available. Methods Long-term follow-up was ...evaluated from 5.0 to 24 years (median, 14 years) after diagnosis in 13 patients with homozygous (n = 10) or compound heterozygous (n = 3) mutations. Results Medical treatment at last follow-up control included supplementation with potassium in 12 patients and sodium in 2 patients and medical treatment with indomethacin in 9 patients. At the end of follow-up, body height was 2.0 standard deviation score or less in 6 patients; 2 of these patients had growth hormone deficiency. Body weight (≤2.0 standard deviation score in 6 patients) significantly increased ( P < 0.05) at the end of follow-up in comparison to values at diagnosis. Nonpostural persistent proteinuria was present in 6 patients, and 4 patients had a glomerular filtration rate less than 75 mL/min/1.73 m2 (<1.25 mL/s). Conclusion These data show that some patients with biallelic mutations in the chloride channel gene CLCNKB tend to present with pathological proteinuria and impaired kidney function after a median follow-up of 14 years, and growth retardation is common and sometimes related to growth hormone deficiency in these patients.
How much vitamin D for children? Pela, Ivana
Clinical cases in mineral and bone metabolism,
05/2012, Volume:
9, Issue:
2
Journal Article
Peer reviewed
Recently a number of studies have reported worldwide recrudescence of biochemical and clinical rickets, despite continuous revisions of the experts about the adequate intake of vitamin D for infants ...and children to maintain an adequate 25-hydroxyvitamin D status and assure the achievement of peak bone mass during the growth. The aim of this review is to illustrate the current opinions and controversies about what should be considered the normal range for serum 25-hydroxyvitamin D concentrations and which doses of vitamin D supplements should be recommended in the various pediatric ages and in different contests as climatic regions, colour of skin and sunlight exposure.
Neuroblastoma is the most common extracranial solid tumor in childhood. Its presenting signs and symptoms may be highly variable, depending on the location of the primary tumor and its local or ...metastatic diffusion and, rarely, with paraneoplastic syndrome such as opsoclonus-myoclonus-ataxia syndrome and gastrointestinal disturbances, due to autoantibodies or to aberrant secretion of vasoactive intestinal peptide. Herein we describe a 10-month-old child with neuroblastoma presenting with a complex clinical picture characterized by acute kidney injury manifested by renal insufficiency and signs and symptoms of tubulointerstitial damage, with polyuria, polydipsia, glucosuria, aminoaciduria and hypochloremic metabolic alkalosis, and of glomerular damage with heavy proteinuria. Imaging study documented a suprarenal mass enveloping the aorta and its abdominal and renal ramifications and bilaterally renal veins. This clinical picture shows some analogies with the hyponatremic-hypertensive syndrome concerning the renovascular disease; however, in absence of systemic arterial hypertension, the heavy proteinuria and the polyuria could be explained by sectional increased intraglomerular pressure, due to local renal blood vessels constriction. Hypochloremic metabolic alkalosis probably developed because of local production of renin, responsible of renin-angiotensin-aldosterone system activation, but above all because of chloride loss through sweating. The long lasting dehydration, due to vomiting, sweating and polyuria, caused prolonged prerenal failure evolving in proximal tubular damage manifestations.
「Introduction」 The Familial hyperkalemic hypertension (FHHt) syndrome (OMIM #145260), first described in 1964, and also known as Gordon's syndrome or pseudohypoaldosteronism type II (PHA II), is a ...rare autosomal dominant disease characterized by hypertension, hyperkalemia, hyperchloremic metabolic acidosis, and normal renal and adrenal function, with suppressed plasma rennin activity. Thiazides correct the metabolic abnormalities and hypertension (1-3). FHHt syndrome may be due to mutations in the WNK1 and WNK4 genes, encoding the with-nolysine kinases 1 and 4 respectively. WNK4 mutants fail to inhibit the thiazide-sensitive Na-Cl cotransporter (NCC), increasing reabsorption of chloride in the distal collecting tubule and causing volume expansion and hypertension, and fail to inhibit the ROMK1 channel, causing hyperkalemia. WNK1 mutants also cause an increase in chloride adsorption both through the activation of EnaC and reduced inhibition of NCC through its influence on the WNK4 activity (4-6).
When he was 15 years old, for the appearance of chronic allograft nephropathy, he started again on peritoneal dialysis and the immunosuppressive treatment was interrupted. Because of frequent ...peritoneal and urinary tract bacterial infections, immunologic laboratory investigations were performed. ...autoimmune manifestations may follow influenza vaccination also in young people if predisposing factors are present.
PDF
