Adult-onset eculizumab-resistant hemolytic uremic syndrome associated with cobalamin C deficiency.

[homocystinuria without methylmalonic aciduria]

A 20 -year -old man was hospitalized for malignant hypertension , mechanical hemolysis , and kidney failure . Kidney biopsy confirmed glomerular and arteriolar thrombotic microangiopathy . Etiologic analyses , which included ADAMTS 13 activity , stool culture , complement factor proteins (C 3 , C 4 , factor H , factor I , and MCP [membrane cofactor protein ]), anti-factor H antibodies , HIV (human immunodeficiency virus ) serology , and antinuclear and antiphospholipid antibodies , returned normal results . Malignant hypertension was diagnosed . Ten months later , we observed a relapse of acute kidney injury and mechanical hemolysis . Considering a diagnosis of complement dysregulation-related atypical hemolytic uremic syndrome (HUS ), we began treatment with eculizumab . Despite the efficient complement blockade , the patient 's kidney function continued to decline . We performed additional analyses and found that the patient 's homocysteine levels were dramatically increased , with no vitamin B 12 (cobalamin ) or folate deficiencies . We observed very low plasma methionine levels associated with methylmalonic aciduria , which suggested cobalamin C disease . We stopped the eculizumab infusions and initiated specific treatment , which resulted in complete cessation of hemolysis . MMACHC (methylmalonic aciduria and homocystinuria type C protein ) sequencing revealed compound heterozygosity for 2 causative mutations . To our knowledge , this is the first report of adult-onset cobalamin C-related HUS . Considering the wide availability and low cost of the homocysteine assay , we suggest that it be included in the diagnostic algorithm for adult patients who present with HUS .

Diseases
Validation

Diseases presenting "hypertension" symptom

achondroplasia

acute rheumatic fever

adrenal incidentaloma

aniridia

aromatase deficiency

cadasil

child syndrome

cohen syndrome

congenital adrenal hyperplasia

congenital diaphragmatic hernia

cushing syndrome

cystinuria

erdheim-chester disease

erythropoietic protoporphyria

esophageal adenocarcinoma

fabry disease

familial hypocalciuric hypercalcemia

gm1 gangliosidosis

heparin-induced thrombocytopenia

hereditary cerebral hemorrhage with amyloidosis

holt-oram syndrome

homocystinuria without methylmalonic aciduria

hydrocephalus with stenosis of the aqueduct of sylvius

inclusion body myositis

kallmann syndrome

kindler syndrome

lamellar ichthyosis

lymphangioleiomyomatosis

pendred syndrome

primary effusion lymphoma

scrub typhus

severe combined immunodeficiency

sneddon syndrome

typhoid

von hippel-lindau disease

well-differentiated liposarcoma

werner syndrome

x-linked adrenoleukodystrophy

zellweger syndrome

This symptom has already been validated