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The phenotypic spectrum of organic acidurias and urea cycle disorders. Part 2: the evolving clinical phenotype
Author(s) -
Kölker Stefan,
Valayannopoulos Vassili,
Burlina Alberto B.,
SykutCegielska Jolanta,
Wijburg Frits A.,
Teles Elisa Leão,
Zeman Jiri,
DionisiVici Carlo,
Barić Ivo,
Karall Daniela,
Arnoux JeanBaptiste,
Avram Paula,
Baumgartner Matthias R.,
BlascoAlonso Javier,
Boy S. P. Nikolas,
Rasmussen Marlene Bøgehus,
Burgard Peter,
Chabrol Brigitte,
Chakrapani Anupam,
Chapman Kimberly,
Cortès i Saladelafont Elisenda,
Couce Maria L.,
Meirleir Linda,
Dobbelaere Dries,
Furlan Francesca,
Gleich Florian,
González Maria Julieta,
Gradowska Wanda,
Grünewald Stephanie,
Honzik Tomas,
Hörster Friederike,
Ioannou Hariklea,
Jalan Anil,
Häberle Johannes,
Haege Gisela,
Langereis Eveline,
Lonlay Pascale,
Martinelli Diego,
Matsumoto Shirou,
Mühlhausen Chris,
Murphy Elaine,
Baulny Hélène Ogier,
Ortez Carlos,
Pedrón Consuelo C.,
PintosMorell Guillem,
PenaQuintana Luis,
Ramadža Danijela Petković,
Rodrigues Esmeralda,
SchollBürgi Sabine,
Sokal Etienne,
Summar Marshall L.,
Thompson Nicholas,
Vara Roshni,
Pinera Inmaculada Vives,
Walter John H.,
Williams Monique,
Lund Allan M.,
Garcia Cazorla Angeles
Publication year - 2015
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-015-9840-x
Subject(s) - medicine , urea cycle , methylmalonic aciduria , encephalopathy , failure to thrive , pediatrics , newborn screening , physiology , endocrinology , methylmalonic acid , genetics , vitamin b12 , biology , amino acid , arginine
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.