title: Neonatal-onset propionic acidemia: neurologic and developmental profiles, and implications for management.
abstract: OBJECTIVE
  To document the clinical and neurodevelopmental profiles of a cohort of patients with neonatal-onset propionic acidemia and to determine the efficacy of current therapy with respect to outcome.
  
  
  METHODS
  The clinical, neurologic, and developmental status of six patients was prospectively evaluated during a 15-month period. Previous clinical and biochemical data were ascertained from hospital records to determine longitudinal nutritional status, number of episodes of hyperammonemia with ketoacidosis, and developmental performance with respect to age.
  
  
  RESULTS
  No deaths resulted from propionic acidemia since the identification of the oldest patient in the series in 1980. Therapeutic intervention (e.g., gastrostomy tube feeding) resulted in improved nutritional status and possibly contributed to improved survival. All children had hypotonia, resulting in a significant effect on motor development; however, focal neurologic deficits and evidence of movement or seizure disorder were absent. Mild cortical atrophy was evident on cranial magnetic resonance imaging in four patients. All children, including two patients with no significant episodes of hyperammonemia and normal growth since the neonatal period, had a mild to moderate degree of intellectual impairment.
  
  
  CONCLUSIONS
  The results of our study suggest that current therapy for neonatal-onset propionic acidemia is associated with improved survival and nutritional status, and an absence of focal neurologic deficits. However, hypotonia and cognitive delay were still present, even in children with "optimal" metabolic control. Additional therapeutic advances are required to improve the developmental and cognitive outcome.
authors.affiliation: Department of Medicine, Children's Hospital, Boston, Massachusetts, USA.
authors.forename: K N
authors.initials: KN
authors.lastname: North
authors.forename: M S
authors.initials: MS
authors.lastname: Korson
authors.forename: Y R
authors.initials: YR
authors.lastname: Gopal
authors.forename: F J
authors.initials: FJ
authors.lastname: Rohr
authors.forename: T B
authors.initials: TB
authors.lastname: Brazelton
authors.forename: S E
authors.initials: SE
authors.lastname: Waisbren
authors.forename: M L
authors.initials: ML
authors.lastname: Warman
mesh_terms: D002262:Carboxy-Lyases / Q000172:deficiency; D002648:Child; D002675:Child, Preschool; D003072:Cognition Disorders / Q000209:etiology; D002658:Developmental Disabilities / Q000209:etiology; D004750:Enteral Nutrition; D005260:Female; D005774:Gastrostomy; D006801:Humans; D007223:Infant; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase; D009129:Muscle Tonus; D009752:Nutritional Status; D011422:Propionates / Q000097:blood*; D011446:Prospective Studies
chemical_list: D011422:Propionates; D002262:Carboxy-Lyases; D043586:Methylmalonyl-CoA Decarboxylase; C029658:propionic acid