1Department of Internal Medicine, School of Medicine, CHA University, Seongnam, Korea.
2Institute for Clinical Research, Korea University College of Medicine, Seoul, Korea.
3Laboratory Medicine, School of Medicine, CHA University, Seongnam, Korea.
4Department of Internal Medicine, Korea University College of Medicine, Seoul, Korea.
Atypical HUS (aHUS), which comprises 5–10% of HUS cases, is not associated with a prodrome of diarrhea and has a worse prognosis than that caused by STEC-HUS . Uncontrolled complement activation, whether sporadic or familial, plays a major role in the pathogenesis of aHUS. Genetic abnormalities in the complement system that lead to uncontrolled complement activation have been demonstrated in 60% of aHUS cases . The most common mutation in aHUS occurs in
A 66-year-old woman was admitted to the hospital owing to altered mental status. She had previously been diagnosed with systemic lupus erythematosus (SLE) and diabetes mellitus and was on medications. She was treated with a 1,000 mg intravenous steroid pulse regimen for cerebral infarction and SLE. Five days after steroid treatment, she was discharged home with clinical improvement.
A month after the discharge, her mental status became aggravated again and was re-admitted to the department of nephrology under the impression of thrombotic thrombocytopenic purpura. Her complete blood count showed a hemoglobin level of 11.2 g/dL, reticulocyte count of 0.2%, platelet count of 60,000 /mm3, and white blood cell count of 13,450/mm3. The prothrombin time was 12 s, and the activated partial thromboplastin time was 42 s. The peripheral blood smear revealed many schistocytes. In the blood chemistry, her blood urea nitrogen and creatinine levels were increased to 46.3 mg/dL and 1.25 mg/dL, respectively. Her total and direct bilirubin levels were 0.58 mm/dL and 0.19 mm/dL, respectively. Her lactated dehydrogenase (LDH) level was elevated to 1,192 U/L. The complement levels (reference ranges in parentheses) were as follows: C3, 40.1 mg/dL (90–180 mg/dL) and C4, 17.9 mg/dL (16–49 mg/dL). Brain MRI showed a subtle diffusion-restricted lesion in the right corpus callosum and left cerebellum, suggestive of cerebral infarction. The ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity was within the normal range. She had no history of bloody diarrhea. The Shiga-toxin assay on stool samples showed negative results. Immediately after admission, the patient received plasma exchange (daily for 2 days), followed by hemodialysis and steroids, and her consciousness improved to the level that she could recognize her family. The hemoglobin, platelet, and creatinine levels recovered to the normal range. Her LDH level also decreased to 456 U/L. The patient completely recovered and was discharged 56 days after admission. She is currently doing well without recurrence of disease under outpatient management on day 340 after the initial diagnosis.
Genomic DNA was extracted from the patient's peripheral blood leukocytes using a G-DEX II Genomic DNA Extraction Kit (iNtRON Biotechnology, Korea). For mutation detection, the coding exons and intron flanking regions of
To the best of our knowledge, this is the first case report of a Korean patient with aHUS associated with the
The mutation was first demonstrated in an 8-month-old Japanese male infant, who had developed aHUS after cardiac surgery . The infant died because of progressive renal and neurologic damage on postoperative day 50. Plasma infusions and hemodialysis were not effective. The response rate to short-term plasma therapy is known to be 40–50% . In contrast, our patient experienced less severe renal damage than the infant and was responsive to plasma exchange. It suggests that the clinical response to plasma therapy in patients with a
Recently, eculizumab, a humanized monoclonal antibody that blocks complement C5 activation and the formation of the terminal complement component, has been widely used for the treatment of aHUS in the USA, Europe, and Japan. Eculizumab has been reported to induce long-term remission in patients with aHUS associated with
Restriction fragment length polymorphism analysis of our patient with heterozygote
Abbreviations: P, patient; WT, wild type.
Localization of the R425C