Do not Miss Rare and Treatable Cause of Early-Onset Hemolytic Uremic Syndrome: Cobalamin C Deficiency

The most common disorder of vitamin B12 metabolism is methylmalonic aciduria and homocystinuria type cobalamin C (cblC), which accounts for most of the cases is referred to as cblC deficiency. Cobalamin deficiency is one of the causes of early-onset hemolytic uremic syndrome (HUS). Here, we present the cases of 2 infants with cobalamin deficiency who presented with early-onset HUS. The first patient was a 5-month-old female who was admitted to the hospital with seizure, pallor, and yellow-colored diarrheal stools. Initial laboratory examination showed direct Coombs test-negative hemolytic anemia. Later, she developed acute kidney injury and thrombocytopenia. Bone marrow aspiration showed megaloblastic features, and urinary examination showed elevated levels of methylmalonic acid (MMA), methyl citrate, and 3-hydroxypropionic acid. Methionine-restricted diet, parenteral hydroxocobalamine, folinic acid, carnitine, and betaine were initiated. Hemolytic activity was controlled with this treatment. Genetic screening showed homozygous mutation on the MMACHCgene (p.R161*[c.481C>T]). The second patient was a 3-month-old male infant who was admitted to the hospital with malaise and diarrhea. Laboratory examination showed direct Coombs test-negative hemolytic anemia with leukopenia. Later he developed acute kidney injury and thrombocytopenia. Bone marrow aspiration revealed megaloblastic changes. Urine organic acid test showed increased levels of MMA. Parenteral hydroxocobalamine, folinic acid, carnitine, and betaine were initiated. He died due to respiratory failure and cardiac arrest. Direct sequencing of MMACHC identified homozygous mutation, c.271dup A. CblC deficiency is an important cause of early-onset HUS and prompt diagnosis will provide specific treatment modalities.