title: 3-Methylglutaconic aciduria type I redefined: a syndrome with late-onset leukoencephalopathy.
abstract: OBJECTIVE
  3-Methylglutaconic aciduria type I is a rare inborn error of leucine catabolism. It is thought to present in childhood with nonspecific symptoms; it was even speculated to be a nondisease. The natural course of disease is unknown.
  
  
  METHODS
  This is a study on 10 patients with 3-methylglutaconic aciduria type I. We present the clinical, neuroradiologic, biochemical, and genetic details on 2 new adult-onset patients and follow-up data on 2 patients from the literature.
  
  
  RESULTS
  Two unrelated patients with the characteristic biochemical findings of 3- methylglutaconic aciduria type I presented in adulthood with progressive ataxia. One patient additionally had optic atrophy, the other spasticity and dementia. Three novel mutations were found in conserved regions of the AUH gene. In both patients, MRI revealed extensive white matter disease. Follow-up MRI in a 10-year-old boy, who presented earlier with isolated febrile seizures, showed mild abnormalities in deep white matter.
  
  
  CONCLUSIONS
  We define 3-methylglutaconic aciduria type I as an inborn error of metabolism with slowly progressive leukoencephalopathy clinically presenting in adulthood. In contrast to the nonspecific findings in pediatric cases, the clinical and neuroradiologic pattern in adult patients is highly characteristic. White matter abnormalities may already develop in the first decades of life. The variable features found in affected children may be coincidental. Long-term follow-up in children is essential to learn more about the natural course of this presumably slowly progressive disease. Dietary treatment with leucine restriction may be considered.
authors.affiliation: Radboud University Nijmegen Medical Centre, Department of Laboratory Medicine, Laboratory of Genetic, Endocrine and Metabolic Diseases (830), PO Box 9101, 6500 HB Nijmegen, the Netherlands.
authors.forename: S B
authors.initials: SB
authors.lastname: Wortmann
authors.forename: B H
authors.initials: BH
authors.lastname: Kremer
authors.forename: A
authors.initials: A
authors.lastname: Graham
authors.forename: M A
authors.initials: MA
authors.lastname: Willemsen
authors.forename: F J
authors.initials: FJ
authors.lastname: Loupatty
authors.forename: S L
authors.initials: SL
authors.lastname: Hogg
authors.forename: U F
authors.initials: UF
authors.lastname: Engelke
authors.forename: L A
authors.initials: LA
authors.lastname: Kluijtmans
authors.forename: R J
authors.initials: RJ
authors.lastname: Wanders
authors.forename: S
authors.initials: S
authors.lastname: Illsinger
authors.forename: B
authors.initials: B
authors.lastname: Wilcken
authors.forename: J R
authors.initials: JR
authors.lastname: Cruysberg
authors.forename: A M
authors.initials: AM
authors.lastname: Das
authors.forename: E
authors.initials: E
authors.lastname: Morava
authors.forename: R A
authors.initials: RA
authors.lastname: Wevers
mesh_terms: D000328:Adult; D000592:Amino Acid Metabolism, Inborn Errors / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D020739:Brain Diseases, Metabolic, Inborn / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D001931:Brain Mapping; D002648:Child; D018450:Disease Progression; D005260:Female; D005977:Glutarates / Q000378:metabolism*; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007223:Infant; D007930:Leucine / Q000378:metabolism*; D056784:Leukoencephalopathies / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology*
chemical_list: D005977:Glutarates; D007930:Leucine