ABSTRACT
BACKGROUND: We report the case of a patient with Shiga toxin (Stx)-associated hemolytic-uremic syndrome (HUS) (STEC-HUS) with a concomitant heterozygous mutation of the gene coding for complement Factor H (CFH). CASE DIAGNOSIS/TREATMENT: An 18-month-old patient presented with hemolytic anemia and thrombotic microangiopathy in the context of acute gastroenteritis. While the patient did not show kidney or other organ failure, he had persistent hemolysis and complement 3 activation (low C3), leading to the decision to commence immunotherapy with eculizumab (Soliris®) together with transient antibiotic coverage and meningococcal vaccination. Patient outcome was favorable. Diagnostic work-up identified Escherichia coli-associated Type 2 Shiga toxin. Complement analysis showed a heterozygous mutation of the CFH gene (c.2103 G>A, p. Trp701X) resulting in a quantitative CFH defect. CONCLUSIONS: We report a case of STEC-HUS with a quantitative CFH defect caused by a mutation of the CFH gene. To the best of our knowledge, very few cases of STEC-HUS with complement gene mutation have been reported, but none to date with a CFH mutation. We therefore suggest that complement analyses be performed in patients diagnosed with STEC-HUS in association with low C3 levels, especially in patients presenting with severe or unexpected clinical symptoms.
Subject(s)
Escherichia coli Infections/microbiology , Hemolytic-Uremic Syndrome/genetics , Hemolytic-Uremic Syndrome/microbiology , Mutation , Shiga-Toxigenic Escherichia coli/pathogenicity , Adolescent , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Biomarkers/blood , Complement C3/analysis , Complement Factor H/genetics , DNA Mutational Analysis , Escherichia coli Infections/complications , Escherichia coli Infections/diagnosis , Escherichia coli Infections/drug therapy , Genetic Markers , Genetic Predisposition to Disease , Hemolytic-Uremic Syndrome/blood , Hemolytic-Uremic Syndrome/diagnosis , Hemolytic-Uremic Syndrome/drug therapy , Heterozygote , Humans , Immunologic Factors/therapeutic use , Male , Meningococcal Vaccines/therapeutic use , Phenotype , Risk Factors , Treatment OutcomeABSTRACT
Nephrolithiasis associated with inborn metabolic diseases is a very rare condition with some common characteristics: early onset of symptoms, family history, associated tubular impairment, bilateral, multiple and recurrent stones, and association with nephrocalcinosis. The prognosis of such diseases may lead to life threatening conditions, not only because of unabated kidney damage but also because of progressive extra-renal involvement, either in a systemic form (e.g. primary hyperoxaluria type 1, requiring combined liver and kidney transplantation), or in a neurological form (Lesch-Nyhan syndrome leading to auto-mutilation and disability, phosphoribosyl pyrophosphate synthetase superactivity, which is associated with mental retardation). Patients with other inborn metabolic diseases present only with recurrent stone formation, such as cystinuria, adenine phosphoribosyl-transferase deficiency, xanthine deficiency. Finally, nephrolithiasis may be secondarily part of some other metabolic diseases, such as glycogen storage disease type 1 or inborn errors of metabolism leading to Fanconi syndrome (nephropathic cystinosis, tyrosinaemia type 1, fructose intolerance, Wilson disease, respiratory chain disorders, etc.). The diagnosis is based on highly specific investigations, including crystal identification, biochemical analyses and DNA study. The treatment of nephrolithiasis requires hydration as well as specific measures. Compliance is a major issue regarding the progression of renal damage, but the overall outcome mainly depends on extra-renal involvement in relation to the metabolic defect.
Subject(s)
Metabolism, Inborn Errors/complications , Nephrolithiasis/etiology , Amino Acid Metabolism, Inborn Errors/complications , Amino Acid Metabolism, Inborn Errors/genetics , Amino Acid Metabolism, Inborn Errors/metabolism , Child , Glycogen Storage Disease Type I/complications , Glycogen Storage Disease Type I/genetics , Glycogen Storage Disease Type I/metabolism , Humans , Hyperoxaluria/etiology , Hyperoxaluria/genetics , Metabolism, Inborn Errors/genetics , Nephrolithiasis/genetics , Purine-Pyrimidine Metabolism, Inborn Errors/complications , Purine-Pyrimidine Metabolism, Inborn Errors/genetics , Purine-Pyrimidine Metabolism, Inborn Errors/metabolismABSTRACT
Human herpesvirus 6 (HHV-6) infection can induce unusual complications in transplant patients, such as interstitial pneumonitis, encephalitis and marrow aplasia. We describe the clinical course of HHV-6 infection in a girl with renal transplantation. She presented with diarrhea and poor feeding on day 36 post-transplantation (Tx), after a 5-day steroid pulse for clinical signs of acute rejection. A week later she developed fever and had elevated plasma creatinine and lactic dehydrogenase levels, but a physical examination did not reveal any anomalies with respect to suggest rash, pneumonitis, encephalitis or lymphadenopathy. Two weeks later, the patient developed anemia and leucopenia. HHV-6 was the only pathogen detected by the PCR assay of the serum and marrow aspiration. The patient had a successful recovery without specific treatment. This case report highlights the wide spectrum of complications resulting from HHV-6 infection in immunosuppressed patients.
