@article{3076496,
    title = "Brain MR patterns in inherited disorders of monoamine neurotransmitters: An analysis of 70 patients",
    author = "Kuseyri Hübschmann, O. and Mohr, A. and Friedman, J. and Manti, F. and Horvath, G. and Cortès-Saladelafont, E. and Mercimek-Andrews, S. and Yildiz, Y. and Pons, R. and Kulhánek, J. and Oppebøen, M. and Koht, J.A. and Podzamczer-Valls, I. and Domingo-Jimenez, R. and Ibáñez, S. and Alcoverro-Fortuny, O. and Gómez-Alemany, T. and de Castro, P. and Alfonsi, C. and Zafeiriou, D.I. and López-Laso, E. and Guder, P. and Santer, R. and Honzík, T. and Hoffmann, G.F. and Garbade, S.F. and Sivri, H.S. and Leuzzi, V. and Jeltsch, K. and García-Cazorla, A. and Opladen, T. and Harting, I. and International Working Group on Neurotransmitter Related Disorders (iNTD)",
    journal = "Journal of Inherited Metabolic Disease",
    year = "2021",
    volume = "44",
    number = "4",
    pages = "1070-1082",
    publisher = "John Wiley and Sons Inc",
    issn = "0141-8955",
    doi = "10.1002/jimd.12360",
    keywords = "Article;  brain atrophy;  brain disease;  child;  clinical evaluation;  differential diagnosis;  diffusion weighted imaging;  dihydropteridine reductase deficiency;  disease severity;  enzyme deficiency;  female;  genetic disorder;  gray matter;  human;  hypoxic ischemic encephalopathy;  infant;  inherited monoamine neurotransmitter disorder;  major clinical study;  male;  medical record;  monoamine oxidase A deficiency;  neuroimaging;  nuclear magnetic resonance imaging;  pediatrics;  T1 weighted imaging;  T2 weighted imaging;  tetrahydrobiopterin deficiency;  tyrosine hydroxylase deficiency;  adolescent;  adult;  brain;  brain mapping;  diagnostic imaging;  disorders of amino acid and protein metabolism;  middle aged;  pathology;  preschool child;  procedures;  retrospective study;  young adult, Adolescent;  Adult;  Amino Acid Metabolism, Inborn Errors;  Brain;  Brain Mapping;  Child;  Child, Preschool;  Female;  Humans;  Infant;  Magnetic Resonance Imaging;  Male;  Middle Aged;  Retrospective Studies;  Young Adult",
    abstract = "Inherited monoamine neurotransmitter disorders (iMNDs) are rare disorders with clinical manifestations ranging from mild infantile hypotonia, movement disorders to early infantile severe encephalopathy. Neuroimaging has been reported as non-specific. We systematically analyzed brain MRIs in order to characterize and better understand neuroimaging changes and to re-evaluate the diagnostic role of brain MRI in iMNDs. 81 MRIs of 70 patients (0.1-52.9 years, 39 patients with tetrahydrobiopterin deficiencies, 31 with primary disorders of monoamine metabolism) were retrospectively analyzed and clinical records reviewed. 33/70 patients had MRI changes, most commonly atrophy (n = 24). Eight patients, six with dihydropteridine reductase deficiency (DHPR), had a common pattern of bilateral parieto-occipital and to a lesser extent frontal and/or cerebellar changes in arterial watershed zones. Two patients imaged after acute severe encephalopathy had signs of profound hypoxic-ischemic injury and a combination of deep gray matter and watershed injury (aromatic l-amino acid decarboxylase (AADCD), tyrosine hydroxylase deficiency (THD)). Four patients had myelination delay (AADCD; THD); two had changes characteristic of post-infantile onset neuronal disease (AADCD, monoamine oxidase A deficiency), and nine T2-hyperintensity of central tegmental tracts. iMNDs are associated with MRI patterns consistent with chronic effects of a neuronal disorder and signs of repetitive injury to cerebral and cerebellar watershed areas, in particular in DHPRD. These will be helpful in the (neuroradiological) differential diagnosis of children with unknown disorders and monitoring of iMNDs. We hypothesize that deficiency of catecholamines and/or tetrahydrobiopterin increase the incidence of and the CNS susceptibility to vascular dysfunction. © 2021 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM."
}