TY - JOUR
T1 - The phenotypic spectrum of organic acidurias and urea cycle disorders Part 2: the evolving clinical phenotype
AU - Kölker, Stefan
AU - Valayannopoulos, Vassili
AU - Burlina, Alberto B.
AU - Sykut-Cegielska, Jolanta
AU - Wijburg, Frits A.
AU - Teles, Elisa Leão
AU - Zeman, Jiri
AU - Dionisi-Vici, Carlo
AU - Barić, Ivo
AU - Karall, Daniela
AU - Arnoux, Jean-Baptiste
AU - Avram, Paula
AU - Baumgartner, Matthias R.
AU - Blasco-Alonso, Javier
AU - Boy, S. P. Nikolas
AU - Rasmussen, Marlene Bøgehus
AU - Burgard, Peter
AU - Chabrol, Brigitte
AU - Chakrapani, Anupam
AU - Chapman, Kimberly
AU - Cortès I Saladelafont, Elisenda
AU - Couce, Maria L.
AU - de Meirleir, Linda
AU - Dobbelaere, Dries
AU - Furlan, Francesca
AU - Gleich, Florian
AU - González, Maria Julieta
AU - Gradowska, Wanda
AU - Grünewald, Stephanie
AU - Honzik, Tomas
AU - Hörster, Friederike
AU - Ioannou, Hariklea
AU - Jalan, Anil
AU - Häberle, Johannes
AU - Haege, Gisela
AU - Langereis, Eveline
AU - de Lonlay, Pascale
AU - Martinelli, Diego
AU - Matsumoto, Shirou
AU - Mühlhausen, Chris
AU - Murphy, Elaine
AU - de Baulny, Hélène Ogier
AU - Ortez, Carlos
AU - Pedrón, Consuelo C.
AU - Pintos-Morell, Guillem
AU - Pena-Quintana, Luis
AU - Ramadža, Danijela Petković
AU - Rodrigues, Esmeralda
AU - Scholl-Bürgi, Sabine
AU - Sokal, Etienne
AU - Summar, Marshall L.
AU - Thompson, Nicholas
AU - Vara, Roshni
AU - Pinera, Inmaculada Vives
AU - Walter, John H.
AU - Williams, Monique
AU - Lund, Allan M.
AU - Garcia-Cazorla, Angeles
AU - Garcia Cazorla, Angeles
PY - 2015
Y1 - 2015
N2 - Background The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. Aims To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. Results Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QT(c) interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. Conclusions Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases
AB - Background The disease course and long-term outcome of patients with organic acidurias (OAD) and urea cycle disorders (UCD) are incompletely understood. Aims To evaluate the complex clinical phenotype of OAD and UCD patients at different ages. Results Acquired microcephaly and movement disorders were common in OAD and UCD highlighting that the brain is the major organ involved in these diseases. Cardiomyopathy [methylmalonic (MMA) and propionic aciduria (PA)], prolonged QT(c) interval (PA), optic nerve atrophy [MMA, isovaleric aciduria (IVA)], pancytopenia (PA), and macrocephaly [glutaric aciduria type 1 (GA1)] were exclusively found in OAD patients, whereas hepatic involvement was more frequent in UCD patients, in particular in argininosuccinate lyase (ASL) deficiency. Chronic renal failure was often found in MMA, with highest frequency in mut(0) patients. Unexpectedly, chronic renal failure was also observed in adolescent and adult patients with GA1 and ASL deficiency. It had a similar frequency in patients with or without a movement disorder suggesting different pathophysiology. Thirteen patients (classic OAD: 3, UCD: 10) died during the study interval, ten of them during the initial metabolic crisis in the newborn period. Male patients with late-onset ornithine transcarbamylase deficiency were presumably overrepresented in the study population. Conclusions Neurologic impairment is common in OAD and UCD, whereas the involvement of other organs (heart, liver, kidneys, eyes) follows a disease-specific pattern. The identification of unexpected chronic renal failure in GA1 and ASL deficiency emphasizes the importance of a systematic follow-up in patients with rare diseases
U2 - https://doi.org/10.1007/s10545-015-9840-x
DO - https://doi.org/10.1007/s10545-015-9840-x
M3 - Article
C2 - 25875216
SN - 0141-8955
VL - 38
SP - 1059
EP - 1074
JO - Journal of Inherited Metabolic Disease
JF - Journal of Inherited Metabolic Disease
IS - 6
ER -