Clinical Chemistry - Case Study
https://doi.org/10.1093/clinchem/hvad212
A 7-year-old girl, who had been born naturally at 41 weeks from a second pregnancy (body weight 3690 g, Apgar score 10/10), was admitted to the Department of Nephrology with symptoms including diarrhea, vomiting, weakness, and reluctance to eat or drink.
Student Discussion Document (pdf)
Monika Paskudzka, Mariusz Rozwandowicz, Paweł Kozłowski, and Olga Ciepiela
A 7-year-old girl, who had been born naturally at 41 weeks from a second pregnancy (body weight 3690 g, Apgar score 10/10), was admitted to the Department of Nephrology with symptoms including diarrhea, vomiting, weakness, and reluctance to eat or drink. Routine hematology and biochemistry tests showed anemia, thrombocytopenia, hyperbilirubinemia with a predominance of unconjugated bilirubin, hyponatremia, and acute kidney injury with high creatinine and blood urea nitrogen (BUN) concentration. There was significant proteinuria and erythrocyturia on urinalysis. Athrombotic microangiopathy (TMA) was suspected: the differential diagnosis included Shiga-toxin–producing Escherichia coli-associated hemolytic uremic syndrome (STEC-HUS), atypical hemolytic uremic syndrome (aHUS), thrombotic thrombocytopenic purpura (TTP), and autoimmune hemolytic anemia (AIHA).
Before the onset of symptoms, the patient had stayed with family in the countryside, where she had been in contact with farm animals. In light of this history and the presence of diarrhea, STEC-HUS was suspected and a PCR for Shiga-toxin–producing Escherichia coli was requested. To exclude AIHA and TTP, a Coombs test and ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity quantification were also requested. Hemodialysis was initiated on the second day of hospitalization in response to acute renal failure (serum creatinine 7.2 mg/dL [636.5 μmmol/L]; serum BUN 163 mg/dL [58.2 mmol/L]). The urine output (calculated as 1.6 mL/kg body mass/hour with a body mass of 25 kg) was considered normal (reference value: >1 mL/kg body mass/hour; >30 mL/h), and there were no symptoms of pulmonary or peripheral edema. After the initial round of dialysis, the creatinine and BUN concentrations decreased to 4.4 mg/dL (389 μmol/L) and 107 mg/dL (38.2 mmol/L), respectively. In total, 6 hemodialysis procedures were performed, and 6 units of packed red blood cells and 1 unit of platelet concentrate were transfused (for laboratory results).
Results of PCR testing for Shiga-toxin produced by E. coli were double-negative, which allowed us to exclude STEC infection. Moreover, ADAMTS13 activity was 97% (reference interval: 61% to 131%), and the Coombs test was negative. TTP and AIHA were therefore excluded, and aHUS was diagnosed, thereby qualifying the patient for treatment with eculizumab. The first dose of eculizumab (600 mg) was administered on Day 4 of her hospital stay without complications. Routine laboratory tests showed normalization of the hemoglobin concentration and platelet count, as well as improved renal function. However, the total complement (CH50) activity was <12.21 U/mL (reference interval: 41.68 to 95.06 U/mL), which is consistent with complete inhibition of the classical complement pathway. On Day 30 of her admission, it was suggested that the patient might be predisposed to complement-dependent aHUS. Subsequent molecular analysis showed that the patient had biallelic variants in the CD46 and CFH genes, which encode the complement regulatory proteins: membrane cofactor protein (MCP) and complement factor H (CFH), respectively.