|Year : 2021 | Volume
| Issue : 2 | Page : 89-90
An interesting case of neonatal atypical hemolytic–uremic syndrome
Benoy Varghese, Arul Rajagopalan, Arun Prasath, Shiva Kumar Ammayappan
Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India
|Date of Submission||18-Jul-2021|
|Date of Decision||12-Oct-2021|
|Date of Acceptance||12-Nov-2021|
|Date of Web Publication||28-Dec-2021|
Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Atypical hemolytic–uremic syndrome (aHUS) in neonates is a rare entity. We report a neonate with aHUS presenting at 16 days of life. She was diagnosed to have a heterozygous pathogenic variant in the gene encoding factor H and was treated with repeated plasma infusions.
Keywords: Atypical hemolytic–uremic syndrome, factor H, plasma infusions
|How to cite this article:|
Varghese B, Rajagopalan A, Prasath A, Ammayappan SK. An interesting case of neonatal atypical hemolytic–uremic syndrome. Asian J Pediatr Nephrol 2021;4:89-90
|How to cite this URL:|
Varghese B, Rajagopalan A, Prasath A, Ammayappan SK. An interesting case of neonatal atypical hemolytic–uremic syndrome. Asian J Pediatr Nephrol [serial online] 2021 [cited 2022 May 27];4:89-90. Available from: https://www.ajpn-online.org/text.asp?2021/4/2/89/334035
| Introduction|| |
Hemolytic–uremic syndrome (HUS) is defined by the triad of microangiopathic hemolytic anemia, thrombocytopenia, and renal impairment. Atypical HUS (aHUS) occurs due to uncontrolled activation of the alternative complement pathway causing systemic endothelial damage, leading to thrombotic microangiopathy (TMA). Approximately 50%–60% of patients with aHUS are associated with mutations encoding complement regulating factors including factor H, membrane cofactor protein, factor I or thrombomodulin, and activating mutations in C3 and factor B.
| Case Report|| |
A 16-day-old girl, born at 39-week gestation (birth weight 2.7 kg) to third-degree consanguineous parents, presented with complaints of refusal to feed, breathlessness, and decreased urine output. Antenatal ultrasound was normal. She had no family history of kidney disease and was not given any prior medications. On examination, she was pale and blood pressure was 170/100 mm Hg.
The hemoglobin level was 3.7 g/dL, total leukocyte count 29,000/mm3, and platelets 90,000/mm3; urea was 120 mg/dL, creatinine 2.0 mg/dL, sodium 113 mEq/L, and potassium 7.4 mEq/L. Urinalysis showed 3+ proteinuria. Lactate dehydrogenase level was 1300 U/L, with 10% schistocytes in the peripheral smear. Doppler ultrasound revealed kidneys with increased cortical echogenicity and no thrombosis. The blood level of complement C3 was 15.0 mg/dL and C4 was 28 mg/dL; homocysteine level was 8.2 mmol/L and methionine 0.70 μmol/L (normal <0.85 μmol/L). Urine culture showed Klebsiella spp. (>105 CFU/mL), sensitive to meropenem, imipenem, and colistin. The patient was treated with meropenem 20 mg/kg intravenously twice daily for 7 days. Echocardiogram showed concentric left ventricular hypertrophy with severe pulmonary artery hypertension. Anti-factor H antibodies were negative.
The patient was provisionally diagnosed to have aHUS and managed with packed red cells (10 mL/kg) and fresh frozen plasma (20 mL/kg). Clinical exome sequencing revealed a novel heterozygous pathogenic variant in complement factor H (CFH), c.3288G >A, p.Trp1096Ter. Blood pressure was controlled with nifedipine, clonidine, labetalol, and enalapril. After 2 weeks, the patient was discharged with satisfactory urine output and serum creatinine of 0.6 mg/dL.
Over the next 4 weeks, the patient had two more episodes of similar symptoms and was treated with fresh frozen plasma infusions (10 mL/kg). Plasma exchange was not done due to technical difficulties, and eculizumab was not available. After the second relapse, the patient was lost to follow-up, and 4 weeks later, she presented with fever, respiratory distress, and hypotension, which was diagnosed as sepsis. Despite therapy, the patient succumbed to sepsis.
| Discussion|| |
The majority (70%) of children with aHUS have the first episode of the disease before the age of 2 years and 25% before the age of 6 months. An infectious event triggers the onset of aHUS in a large proportion of children. Cobalamin C disorder is also an important cause for neonatal aHUS. Without normal regulation of alternate complement pathway, C3b deposition increases, causing activation of the complement cascade, which remains so until complement components are consumed. CFH mutations are the most common cause of aHUS, accounting for around 45% of familial type and 20% of sporadic type. The frequency of CFH mutations in aHUS is around 20%–30%, and patients may present even at birth. Our patient had a novel heterozygous pathogenic variant in CFH and presented with respiratory distress, hemolytic anemia, and kidney failure at 16 days of life.
Management options include supportive therapy, dialysis if needed, plasma therapy, and eculizumab. Control of hypertension is very difficult in acute stages, and our patient required four antihypertensives, including enalapril. Platelets infusions might worsen the TMA process. Plasma therapy should be started within 24-hr of diagnosis. Plasma exchange (40–60 mL/kg with fresh frozen plasma for restitution) or plasma infusions (10–15 mL/kg) are done during the acute phase, administered daily for at least 5 days and up to a maximum of 2 weeks, and then tapered to long-term maintenance plasma therapy. Although plasma exchange is associated with a reduction of mortality from 50% to 25%, in a 3-year follow-up, 48% of pediatric patients and 67% of adult patients died or progressed to end-stage renal disease. Eculizumab is considered first-line therapy for aHUS, provided other causes of TMA are excluded. In our setting, eculizumab was not available, and the patient was treated with plasma infusions.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Michaux K, Bacchetta J, Javouhey E, Cochat P, Frémaux-Bacchi V, Sellier-Leclerc AL. Eculizumab in neonatal hemolytic uremic syndrome with homozygous factor H deficiency. Pediatr Nephrol 2014;29:2415-9.
Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 2018;13:300-17.
Sellier-Leclerc AL, Fremeaux-Bacchi V, Dragon-Durey MA, Macher MA, Niaudet P, Guest G, et al.
Differential impact of complement mutations on clinical characteristics in atypical hemolytic uremic syndrome. J Am Soc Nephrol 2007;18:2392-400.
Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009;361:1676-87.
Chenel C, Wood C, Gourrier E, Zittoun J, Casadevall I, Ogier H. Neonatal hemolytic-uremic syndrome, methylmalonic aciduria and homocystinuria caused by intracellular vitamin B 12 deficiency. Value of etiological diagnosis. Arch Fr Pediatr 1993;50:749-54.
De S, Waters AM, Segal AO, Trautmann A, Harvey EA, Licht C. Severe atypical HUS caused by CFH S1191L – Case presentation and review of treatment options. Pediatr Nephrol 2010;25:97-104.
Ariceta G, Besbas N, Johnson S, Karpman D, Landau D, Licht C, et al.
Guideline for the investigation and initial therapy of diarrhea-negative hemolytic uremic syndrome. Pediatr Nephrol 2009;24:687-96.
Ariceta G, Arrizabalaga B, Aguirre M, Morteruel E, Lopez-Trascasa M. Eculizumab in the treatment of atypical hemolytic uremic syndrome in infants. Am J Kidney Dis 2012;59:707-10.