Hemolytic uremic syndrome with dual caution in an infant: cobalamin C defect and complement dysregulation successfully treated with eculizumab

Barlas, Ülkem Koçoğlu; Kıhtır, Hasan Serdar; Göknar, Nilüfer; Ersoy, Melike; Akçay, Nihal; Şevketoğlu, Esra

doi:10.1007/s00467-018-3941-3

Cited by 8 publications

(7 citation statements)

References 12 publications

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“…For instance, nonsense mutation c.666C > A is commonly observed in patients with Italian origin, as was the origin of the one patient with the same identified mutation in the present review [29]. Furthermore, nonsense mutation c.481C > T was reported in one Turkish patient and one patient of Oriental origin [19,28,31] and homozygous missense mutation c. 484G > T in two other Turkish patients [14,20]. Interestingly, the latter mutation was not included in the common pathogenic variants of the disease.…”

Section: Discussionsupporting

confidence: 67%

“…Nevertheless, symptoms of cblC defect may initially occur at an older age, while potential misdiagnosis as atypical HUS may result in unnecessarily prolonged treatment with complement blockage factor, delayed diagnosis and subsequent severe complications, such as pulmonary hypertension and relapse of AKI [12,13]. Interestingly, cblC defect has also been identified in a few patients with alternative complement pathway disorders, including an infant with low complement factor H (CFH) activity [14], a child with CFH mutation [15], a child with encoding membrane cofactor protein (CD46) mutation [16] and a young adult with CFH antibody-mediated HUS [17]. Therefore, it seems prudent to perform the widely available and low-cost homocysteine assay as part of the HUS diagnostic workup, regardless of age-onset, and even in cases with defined genetic or acquired alternative complement pathway dysregulation.…”

Section: Discussionmentioning

confidence: 99%

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Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review

et al. 2021

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Methylmalonic acidemia and homocystinuria cobalamin C (cblC) type is the most common inborn error of the intracellular cobalamin metabolism, associated with multisystem involvement and high mortality rates, especially in the early-onset form of the disease. Hemolytic uremic syndrome (HUS) is a rare manifestation and needs to be distinguished from other causes of renal thrombotic microangiopathy. We describe a case of a 3-month-old infant, with failure to thrive, hypotonia and pallor, who developed HUS in the setting of cblC deficit, along with dilated cardiomyopathy, and presented delayed response to optic stimulation in visual evoked potentials, as well as enlarged bilateral subarachnoid spaces and delayed myelination in brain magnetic resonance imaging. Renal damage was reversed, while neurodevelopmental profile and eye contact improved after supplementation with parenteral hydroxycobalamin, oral folic acid, betaine and levocarnitine. Homozygous mutation of c.271dupA in the MMACHC gene was ultimately detected. In this report, we highlight the diagnostic challenges as well as the significance of early recognition and multidisciplinary management of this unusual condition. A brief review of published case reports of early-onset cblC deficit and related HUS is depicted, pointing out the initial clinical presentation, signs of renal damage and outcome, MMACHC gene type of mutations and accompanying extra-renal manifestations.

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Section: Discussionsupporting

confidence: 67%

Section: Discussionmentioning

confidence: 99%

Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review

et al. 2021

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“…She was treated with plasma exchanges and vitamin therapy, which allowed dialysis weaning but was followed by persistent chronic renal failure. The second patient was a 6month-old male infant who had microangiopathy caused by cblC deficiency [10]. Despite vitamin therapy, evolution was not favorable with hemodialysis requirement.…”

Section: Discussionmentioning

confidence: 99%

“…The infant's C3 level was decreased and an alternative complement pathway-associated dysfunction was suspected. Eculizumab was initiated despite there being no abnormalities of the alternative complement pathway detected and dialysis weaning was achieved [10].…”

Section: Discussionmentioning

confidence: 99%

Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult

Philipponnet¹,

Desenclos²,

Braïlova³

et al. 2020

BMC Nephrol

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Background: Thrombotic microangiopathy (TMA) syndromes are characterized by the association of hemolytic anemia, thrombocytopenia and organ injury due to arteriolar and capillary thrombosis. Case presentation: We report the first case of adult onset cobalamin C (Cbl C) disease associated with anti-factor H antibody-associated hemolytic uremic syndrome (HUS). A 19-year-old woman was admitted to the nephrology department owing to acute kidney failure, proteinuria, and hemolytic anemia with schizocytes. TMA was diagnosed and plasma exchanges were started in emergency. Exhaustive analyses showed 1) circulating anti factor H antibody and 2) hyperhomocysteinemia, hypomethioninemia and high levels of methylmalonic aciduria pointing towards Clb C disease. Cbl C disease has been confirmed by methylmalonic aciduria and homocystinuria type C protein gene sequencing revealing two heterozygous pathogenic variants. The kidney biopsy showed 1) intraglomerular and intravascular thrombi 2) noticeable thickening of the capillary wall with a duplication aspect of the glomerular basement membrane and a glomerular capillary wall IgM associated with Cbl C disease related TMA. We initiated treatment including hydroxycobalamin, folinic acid, betaine and levocarnitine and Eculizumab. Rituximab infusions were performed allowing a high decrease in anti-factor H antibody rate. Six month after the disease onset, Eculizumab was weaning and vitaminotherapy continued. Outcome was favorable with a dramatic improvement in kidney function. Conclusion: TMA with renal involvement can have a complex combination of risk factors including anti-FH autoantibody in the presence of cblC deficiency.

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“…In this case the pathogenetic mechanism was analyzed because of the non-response to appropriate metabolic therapy. The child was then treated with eculizumab with good results [ 14 ].…”

Section: Discussionmentioning

confidence: 99%

Favorable course of previously undiagnosed Methylmalonic Aciduria with Homocystinuria (cblC type) presenting with pulmonary hypertension and aHUS in a young child: a case report

et al. 2018

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BackgroundCobalamin C (cblC) defect is the most common inborn error of Vitamin B12 metabolism often causing severe neurological, renal, gastrointestinal and hematological symptoms. Onset with pulmonary hypertension (PAH) and atypical hemolytic-uremic syndrome (aHUS) is rare.Case presentationWe describe the case of a 2-years old child, previously in good health, admitted to the hospital with severe respiratory symptoms, rapid worsening of clinical conditions, O2 desaturation and palmo-plantar edema. The patient showed PAH and laboratory findings compatible with aHUS. cblC defect, an inborn error of metabolism, was identified as the cause of all the symptoms described (cardiac, respiratory and renal involvement). Results of neonatal screening for inborn errors of metabolism had been negative.Administration of IM OHCbl (intramuscular hydroxocobalamin), oral betaine and symptomatic treatment with diuretics and anti-hypertensive systemic and pulmonary drugs induced dramatic improvement of both cardiac and systemic symptoms.ConclusionsIn this case of cblC defect the metabolic treatment completely reverted symptoms of aHUS and PAH. The course was favorable, and the prognosis is what we foresee for the future.

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Hemolytic uremic syndrome with dual caution in an infant: cobalamin C defect and complement dysregulation successfully treated with eculizumab

Abstract: To the best of our knowledge, our patient is the first to have Cbl C defect-HUS accompanied by complement dysregulation, who responded well to eculizumab therapy.

Cited by 8 publications

References 12 publications

Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review

Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review

Cobalamin c deficiency associated with antifactor h antibody-associated hemolytic uremic syndrome in a young adult

Favorable course of previously undiagnosed Methylmalonic Aciduria with Homocystinuria (cblC type) presenting with pulmonary hypertension and aHUS in a young child: a case report

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