title: [Outcomes of patients with combined methylmalonic acidemia and homocystinuria after treatment].
abstract: OBJECTIVE
  Combined methylmalonic acidemia with homocystinuria is a common form of methylmalonic acidemia in China. Patients with this disease can progress to death without timely and effective treatment. This study aimed to analyze the treatment outcomes of patients with combined methylmalonic acidemia and homocystinuria.
  
  
  METHODS
  From September 2004 to April 2012, 58 patients with combined methylmalonic acidemia and homocystinuria (34 males and 24 females) were diagnosed and treated in our hospital. Fifty cases were from clinical patients including 42 early-onset cases and 8 late-onset cases. Their age when they were diagnosed ranged from 18 days to 30.8 years. The other 8 cases were from newborn screening. All the patients were treated with vitamin B12, betaine, folic acid, vitamin B6, and L-carnitine. The physical and neuropsychological development, general laboratory tests, the levels of amino acids, acylcarnitines, and homocysteine in blood, and organic acids in urine were followed up.
  
  
  RESULTS
  The follow-up period ranged from 1 month to 7.1 years. Three cases died (all were early-onset cases). In the other patients after treatment, the symptoms such as recurrent vomiting, seizures, lethargy, and poor feeding disappeared, muscle strength and muscle tension were improved, and general biochemical abnormalities such as anemia and metabolic acidosis were corrected. Among the surviving 55 cases, 49 had neurological impairments such as developmental delay and mental retardation. The median levels of blood propionylcarnitine and its ratio with acetylcarnitine, serum homocysteine, and urine methylmalonic acid were significantly decreased (P < 0.01), from 7.73 µmol/L (ranged from 1.5 to 18.61 µmol/L), 0.74 (ranged from 0.29 to 2.06), 97.3 µmol/L (ranged from 25.1 to 250 µmol/L) and 168.55 (ranged from 3.66 to 1032.82) before treatment to 2.74 µmol/L (ranged from 0.47 to 12.09 µmol/L), 0.16 (ranged from 0.03 to 0.62), 43.8 µmol/L (ranged from 17 to 97.8 µmol/L) and 6.81 (ranged from 0 to 95.43) after treatment, respectively.
  
  
  CONCLUSIONS
  Patients with combined methylmalonic acidemia and homocystinuria respond to a combined treatment consisting of supplementation of hydroxycobalamin, betaine, folic acid, vitamin B6 and L-carnitine with clinical and biochemical improvement. But the long-term outcomes are unsatisfactory, with neurological sequelae in most patients.
authors.affiliation: Department of Pediatric Endocrinologic, Genetic and Metabolic Diseases, Shanghai Institute for Pediatric Research, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China.
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Huang
authors.forename: Lian-shu
authors.initials: LS
authors.lastname: Han
authors.forename: Jun
authors.initials: J
authors.lastname: Ye
authors.forename: Wen-juan
authors.initials: WJ
authors.lastname: Qiu
authors.forename: Hui-wen
authors.initials: HW
authors.lastname: Zhang
authors.forename: Xiao-lan
authors.initials: XL
authors.lastname: Gao
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Wen-jun
authors.initials: WJ
authors.lastname: Ji
authors.forename: Xiao-yan
authors.initials: XY
authors.lastname: Li
authors.forename: Xue-fan
authors.initials: XF
authors.lastname: Gu
mesh_terms: D000293:Adolescent; D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D001622:Betaine / Q000008:administration & dosage / Q000627:therapeutic use; D002331:Carnitine / Q000031:analogs & derivatives / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D005500:Follow-Up Studies; D006711:Homocystine / Q000097:blood; D006712:Homocystinuria / Q000097:blood / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D006879:Hydroxocobalamin / Q000008:administration & dosage / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008764:Methylmalonic Acid / Q000652:urine; D015997:Neonatal Screening; D016896:Treatment Outcome; D014805:Vitamin B 12 / Q000008:administration & dosage / Q000627:therapeutic use*; D014806:Vitamin B 12 Deficiency / Q000151:congenital; D055815:Young Adult
chemical_list: C003223:propionylcarnitine; D001622:Betaine; D006711:Homocystine; D008764:Methylmalonic Acid; D014805:Vitamin B 12; D006879:Hydroxocobalamin; D002331:Carnitine