title: Neonatal atypical hemolytic uremic syndrome due to methylmalonic aciduria and homocystinuria.
abstract: BACKGROUND
  Inborn errors of cobalamin (Cbl) absorption and metabolism form a large group of rare diseases that include Cbl-C disorder. Among the renal complications of Cbl-C disorder, atypical hemolytic uremic syndrome (HUS) is the least common and has been described only in a small number of cases.
  
  
  METHODS
  Four patients were admitted to our clinic after 15-30 days of life with vomiting associated with poor sucking, failure to thrive, lethargy and hypotonia. Examinations showed thrombocytopenia and microangiopathic hemolytic anemia associated with renal damage. The neonates had high blood homocysteine levels, increased urinary levels of both homocystine and methylmalonic acid, increased propionylcarnitine (C3) levels and an increased C3/acetylcarnitine ratio. Homozygosity for c.271-272dupA (p.Arg91LysfsX14) of the MMACHC gene was detected in three patients, and heterozygosity for c.271-272dupA and c.666C > A(p.Tyr222X) in one patient, which confirmed the diagnosis of Cbl-C disorder. Treatment with parenteral hydroxycobalamin in combination with folic acid and betaine gradually normalized the metabolic test findings and hematological and renal parameters after about 1 week.
  
  
  CONCLUSIONS
  Atypical HUS in neonates with Cbl-C disorder may be associated with mild to moderate renal involvement also in early-onset disease, and early adequate therapy can reverse renal damage.
authors.affiliation: Department of Maternal and Pediatric Sciences, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Università degli Studi di Milano, Via Commenda 9, 20122 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Menni
authors.forename: Sara
authors.initials: S
authors.lastname: Testa
authors.forename: Sophie
authors.initials: S
authors.lastname: Guez
authors.forename: Gabriella
authors.initials: G
authors.lastname: Chiarelli
authors.forename: Luisella
authors.initials: L
authors.lastname: Alberti
authors.forename: Susanna
authors.initials: S
authors.lastname: Esposito
mesh_terms: D000592:Amino Acid Metabolism, Inborn Errors / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D065766:Atypical Hemolytic Uremic Syndrome; D002352:Carrier Proteins / Q000235:genetics; D006463:Hemolytic-Uremic Syndrome / Q000209:etiology* / Q000503:physiopathology; D006712:Homocystinuria / Q000150:complications* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010088:Oxidoreductases; D014806:Vitamin B 12 Deficiency / Q000151:congenital
chemical_list: D002352:Carrier Proteins; C508359:MMACHC protein, human; D010088:Oxidoreductases