title: Nephrotic syndrome and thrombotic microangiopathy caused by cobalamin C deficiency.
abstract: BACKGROUND
  Cobalamin C (CblC) defects are inherited autosomal recessive disorders of vitamin B12 metabolism due to mutations in the MMACHC gene. Renal manifestations include thrombotic microangiopathy (TMA), acute or chronic renal failure, tubulointerstitial nephritis, and proximal renal tubular acidosis. However, reports about glomerular pathologies are scarce.
  
  
  METHODS
  A 4-year-old boy presented with nephrotic syndrome, arterial hypertension, and chronic anemia but no signs of hemolysis. Renal biopsy showed TMA with ischemic glomerular collapse, foot process effacement, and tubulointerstitial fibrosis. Elevated serum levels of homocysteine suggested a cobalamin C disorder. This was confirmed by the identification of compound heterozygous mutations in the MMACHC gene. Initial therapy consisted of antihypertensive treatment including angiotensin converting enzyme inhibitor (ACEi) leading to blood pressure control and a significant reduction of proteinuria. After a definite diagnosis of CblC deficiency, hydroxocobalamin was introduced. Thereafter, homocysteine levels decreased, anemia resolved, and a further decline of proteinuria with normalization of serum protein levels was noted. Renal function remained stable.
  
  
  CONCLUSIONS
  Although uncommon, the clinical picture of CblC defects may be ruled by nephrotic syndrome mimicking glomerulonephritis, minimal change disease, or primary focal and segmental glomerulosclerosis. Key to a correct diagnosis is elevated serum levels of homocysteine, and a definite diagnosis can be confirmed by genetic testing.
authors.affiliation: University Children's Hospital Muenster, Muenster, NRW, Germany, jens.koenig@ukmuenster.de.
authors.forename: Jens C
authors.initials: JC
authors.lastname: Koenig
authors.forename: Frank
authors.initials: F
authors.lastname: Rutsch
authors.forename: Clemens
authors.initials: C
authors.lastname: Bockmeyer
authors.forename: Matthias
authors.initials: M
authors.lastname: Baumgartner
authors.forename: Bodo B
authors.initials: BB
authors.lastname: Beck
authors.forename: Brigitta
authors.initials: B
authors.lastname: Kranz
authors.forename: Martin
authors.initials: M
authors.lastname: Konrad
mesh_terms: D000740:Anemia / Q000209:etiology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use; D001706:Biopsy; D002352:Carrier Proteins / Q000235:genetics; D002675:Child, Preschool; D006710:Homocysteine / Q000097:blood; D006801:Humans; D006879:Hydroxocobalamin / Q000627:therapeutic use; D006977:Hypertension, Renal / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D007668:Kidney / Q000473:pathology; D008297:Male; D009404:Nephrotic Syndrome / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D010088:Oxidoreductases; D057049:Thrombotic Microangiopathies / Q000188:drug therapy / Q000209:etiology* / Q000473:pathology; D014805:Vitamin B 12 / Q000378:metabolism*; D014806:Vitamin B 12 Deficiency / Q000150:complications* / Q000235:genetics / Q000473:pathology
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D002352:Carrier Proteins; D006710:Homocysteine; C508359:MMACHC protein, human; D010088:Oxidoreductases; D014805:Vitamin B 12; D006879:Hydroxocobalamin