Atypical hemolytic uremic syndrome induced by CblC subtype of methylmalonic academia: A case report and literature review

Medicine (Baltimore). 2017 Oct;96(43):e8284. doi: 10.1097/MD.0000000000008284.


Rationale: Methylmalonic acidemia (MMA) is a common organic acidemia, mainly due to methylmalonyl-CoA mutase (MCM) or its coenzyme cobalamin (VitB12) metabolic disorders. Cobalamin C (CblC) type is the most frequent inborn error of cobalamin metabolism; it can develop symptoms in childhood and often combine multisystem damage, which leads to methylmalonic acid, propionic acid, methyl citrate, and other metabolites abnormal accumulation, causing nerve, liver, kidney, bone marrow, and other organ damage.

Patient concerns: A 4-year-old girl presented with paleness, fatigue, severe normochromic anemia, and acute kidney injury.

Diagnosis: Based on severe normochromic anemia and acute kidney injury, renal biopsy showed membranous proliferative glomerular lesions and thrombotic microvascular disease, supporting the diagnosis of aHUS. Although the serum vitamin B12 was normal, further investigation found the concentration of urinary methylmalonic acid and serum homocysteine increased obviously, genetic analysis revealed a heterozygous MMACHC mutation (exonl: c. 80A >G, c. 609G >A). The final diagnosis was aHUS induced by inherited methylmalonic acidemia (MMACHC heterozygous mutation exonl: c. 80A >G, c. 609G >A).

Interventions: The patient was treated with a 1mg vitamin B12 intramuscular injection daily for 4 days after which the dose was then adjusted to a 1mg intramuscular injection twice a week. At the same time, the girl was given levocarnitine, betaine, folic acid, along with supportive treatment.

Outcomes: After treated by vitamin B12 for 10 days, the patient condition significantly improved, Follow-up results showed complete recovery of hemoglobin and renal function.

Lessons: Although the majority of MMA onset from neurological damage, our case illustrates that partial CblC-type MMA can onset with severe metabolic aHUS. On the basis of chronic thrombotic microangiopathy (TMA)-induced renal damage, it can be complicated by acute hemolytic lesions. MMA should be considered in those patients with unclear microangiopathic hemolytic anemia accompany significant megaloblastic degeneration in bone marrow. We should pay attention to the causes and adopt a reasonable treatment strategy.

Publication types

  • Case Reports
  • Review

MeSH terms

  • Amino Acid Metabolism, Inborn Errors* / blood
  • Amino Acid Metabolism, Inborn Errors* / complications
  • Amino Acid Metabolism, Inborn Errors* / genetics
  • Atypical Hemolytic Uremic Syndrome* / diagnosis
  • Atypical Hemolytic Uremic Syndrome* / drug therapy
  • Atypical Hemolytic Uremic Syndrome* / etiology
  • Atypical Hemolytic Uremic Syndrome* / physiopathology
  • Carrier Proteins / genetics*
  • Child, Preschool
  • Female
  • Homocysteine / blood
  • Humans
  • Kidney / pathology
  • Methylmalonic Acid / blood
  • Mutation
  • Oxidoreductases
  • Treatment Outcome
  • Vitamin B 12* / administration & dosage
  • Vitamin B 12* / blood
  • Vitamin B 12* / metabolism
  • Vitamin B Complex / administration & dosage


  • Carrier Proteins
  • Homocysteine
  • Vitamin B Complex
  • Methylmalonic Acid
  • MMACHC protein, human
  • Oxidoreductases
  • Vitamin B 12

Supplementary concepts

  • Methylmalonic acidemia