• Users Online: 208
  • Print this page
  • Email this page


 
 
Table of Contents
CASE REPORT
Year : 2021  |  Volume : 4  |  Issue : 2  |  Page : 89-90

An interesting case of neonatal atypical hemolytic–uremic syndrome


Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu, India

Date of Submission18-Jul-2021
Date of Decision12-Oct-2021
Date of Acceptance12-Nov-2021
Date of Web Publication28-Dec-2021

Correspondence Address:
Benoy Varghese
Department of Nephrology, Madurai Medical College, Madurai, Tamil Nadu
India
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ajpn.ajpn_31_21

Rights and Permissions
  Abstract 


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 Jan 17];4:89-90. Available from: https://www.ajpn-online.org/text.asp?2021/4/2/89/334035




  Introduction Top


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).[1] 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.[2]


  Case Report Top


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 Top


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.[3] An infectious event triggers the onset of aHUS in a large proportion of children.[4] Cobalamin C disorder is also an important cause for neonatal aHUS.[5] 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.[4] 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.[6] 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.[7] Eculizumab is considered first-line therapy for aHUS, provided other causes of TMA are excluded.[8] 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

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
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.  Back to cited text no. 1
    
2.
Brocklebank V, Wood KM, Kavanagh D. Thrombotic microangiopathy and the kidney. Clin J Am Soc Nephrol 2018;13:300-17.  Back to cited text no. 2
    
3.
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.  Back to cited text no. 3
    
4.
Noris M, Remuzzi G. Atypical hemolytic-uremic syndrome. N Engl J Med 2009;361:1676-87.  Back to cited text no. 4
    
5.
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.  Back to cited text no. 5
    
6.
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.  Back to cited text no. 6
    
7.
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.  Back to cited text no. 7
    
8.
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.  Back to cited text no. 8
    




 

Top
 
  Search
 
    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

 
  In this article
Abstract
Introduction
Case Report
Discussion
References

 Article Access Statistics
    Viewed144    
    Printed8    
    Emailed0    
    PDF Downloaded16    
    Comments [Add]    

Recommend this journal