title: Highly efficient ketone body treatment in multiple acyl-CoA dehydrogenase deficiency-related leukodystrophy.
abstract: BACKGROUND
  Multiple acyl-CoA dehydrogenase deficiency- (MADD-), also called glutaric aciduria type 2, associated leukodystrophy may be severe and progressive despite conventional treatment with protein- and fat-restricted diet, carnitine, riboflavin, and coenzyme Q10. Administration of ketone bodies was described as a promising adjunct, but has only been documented once.
  
  
  METHODS
  We describe a Portuguese boy of consanguineous parents who developed progressive muscle weakness at 2.5 y of age, followed by severe metabolic decompensation with hypoglycaemia and coma triggered by a viral infection. Magnetic resonance (MR) imaging showed diffuse leukodystrophy. MADD was diagnosed by biochemical and molecular analyses. Clinical deterioration continued despite conventional treatment. Enteral sodium D,L-3-hydroxybutyrate (NaHB) was progressively introduced and maintained at 600 mg/kg BW/d (≈ 3% caloric need). Follow up was 3 y and included regular clinical examinations, biochemical studies, and imaging.
  
  
  RESULTS
  During follow up, the initial GMFC-MLD (motor function classification system, 0 = normal, 6 = maximum impairment) level of 5-6 gradually improved to 1 after 5 mo. Social functioning and quality of life recovered remarkably. We found considerable improvement of MR imaging and spectroscopy during follow up, with a certain lag behind clinical recovery. There was some persistent residual developmental delay.
  
  
  CONCLUSIONS
  NaHB is a highly effective and safe treatment that needs further controlled studies.
authors.affiliation: 1] Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland [2] Institute of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Matthias
authors.initials: M
authors.lastname: Gautschi
authors.affiliation: Institute of Neuroradiology, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Christian
authors.initials: C
authors.lastname: Weisstanner
authors.affiliation: Institute of Neuroradiology, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Johannes
authors.initials: J
authors.lastname: Slotboom
authors.affiliation: Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Esmeralda
authors.initials: E
authors.lastname: Nava
authors.affiliation: Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Theres
authors.initials: T
authors.lastname: Zürcher
authors.affiliation: 1] Department of Paediatrics, University Hospital Bern, Inselspital, Bern, Switzerland [2] Institute of Clinical Chemistry, University Hospital Bern, Inselspital, Bern, Switzerland.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Nuoffer
mesh_terms: D001921:Brain / Q000473:pathology; D002331:Carnitine / Q000737:chemistry; D002675:Child, Preschool; D003128:Coma / Q000150:complications; D003241:Consanguinity; D004041:Dietary Fats; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000378:metabolism*; D006801:Humans; D007003:Hypoglycemia / Q000150:complications; D007659:Ketones / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008297:Male; D054069:Multiple Acyl Coenzyme A Dehydrogenase Deficiency / Q000378:metabolism*; D018908:Muscle Weakness / Q000473:pathology; D012256:Riboflavin / Q000737:chemistry; D016896:Treatment Outcome; D014451:Ubiquinone / Q000031:analogs & derivatives / Q000737:chemistry
chemical_list: D004041:Dietary Fats; D007659:Ketones; D014451:Ubiquinone; C024989:coenzyme Q10; D002331:Carnitine; D012256:Riboflavin