title: MRI and (1)H-MRS in adenosine kinase deficiency.
abstract: BACKGROUND
  Adenosine kinase deficiency (ADK deficiency) is a recently described disorder of methionine and adenosine metabolism resulting in a neurological phenotype with developmental delay, muscular hypotonia, and epilepsy as well as variable systemic manifestations. The underlying neuropathology is poorly understood. We have investigated MRI and (1)H-MRS changes in ADK deficiency in order to better understand the in vivo neuropathologic changes of ADK deficiency.
  
  
  METHODS
  Systematic evaluation of 21 MRIs from eight patients (age range 9 days-14.6 years, mean 3.9 years, median 2.7 years) including diffusion-weighted imaging in six and (1)H-MRS in five patients.
  
  
  RESULTS
  Brain maturation was delayed in the neonatal period and in infancy (6/6), but ultimately complete. White matter changes occurring in five of eight patients were discrete, periventricular, and unspecific (4/5), or diffuse with sparing of optic radiation, corona radiata, and pyramidal tracts (1/5). Choline was low in white matter spectra (3/3), while there was no indication of low creatine in white matter or basal ganglia (5/5), and diffusion was variably decreased or increased. Central tegmental tract hyperintensity was a common finding (6/8), as was supratentorial atrophy (6/8).
  
  
  CONCLUSIONS
  MRI changes in ADK deficiency consist of delayed but ultimately completed brain maturation with later onset of mostly unspecific white matter changes and potentially transient central tegmental tract hyperintensity. Immaturity on neonatal MRI is consistent with prenatal onset of disease and reduced choline with lower membrane turnover resulting in delayed myelination and deficient myelin maintenance.
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: C
authors.initials: C
authors.lastname: Staufner
authors.affiliation: Center for Pediatrics and Adolescent Medicine, University Hospital Freiburg, Freiburg, Germany.
authors.forename: H J
authors.initials: HJ
authors.lastname: Blom
authors.affiliation: Division of Metabolism, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Dionisi-Vici
authors.affiliation: Children's Hospital Reutlingen, Reutlingen, Germany.
authors.forename: P
authors.initials: P
authors.lastname: Freisinger
authors.affiliation: Department of Pediatrics, Jahra Hospital, Jahra, Kuwait.
authors.forename: N
authors.initials: N
authors.lastname: Makhseed
authors.affiliation: Center for Molecular Diseases, CHUV Lausanne, Lausanne, Switzerland.
authors.forename: D
authors.initials: D
authors.lastname: Ballhausen
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Kölker
authors.affiliation: Department of General Pediatrics, Division of Neuropediatrics and Pediatric Metabolic Medicine, University Hospital Heidelberg, Heidelberg, Germany.
authors.forename: G F
authors.initials: GF
authors.lastname: Hoffmann
authors.affiliation: Department of Neuroradiology, University Hospital Heidelberg, Im Neuenheimer Feld 400, 69120, Heidelberg, Germany. inga.harting@med.uni-heidelberg.de.
authors.forename: I
authors.identifier: http://orcid.org/0000-0002-5734-8548
authors.initials: I
authors.lastname: Harting
mesh_terms: D000248:Adenosine Kinase / Q000172:deficiency* / Q000378:metabolism; D000293:Adolescent; D001921:Brain / Q000378:metabolism* / Q000473:pathology*; D001928:Brain Diseases, Metabolic / Q000201:enzymology* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D057054:Molecular Imaging / Q000379:methods; D066244:Proton Magnetic Resonance Spectroscopy / Q000379:methods*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity
chemical_list: D000248:Adenosine Kinase
keywords: Adenosine kinase deficiency; Brain maturation; Diffusion-weighted imaging; Magnetic resonance spectroscopy; Neurometabolic disorders