TY - JOUR
T1 - Long-term effects of medical management on growth and weight in individuals with urea cycle disorders
AU - European registry and network for Intoxication type Metabolic Diseases (E-IMD)
AU - Urea Cycle Disorders Consortium (UCDC)
AU - Posset, Roland
AU - Garbade, Sven F.
AU - Gleich, Florian
AU - Gropman, Andrea L.
AU - de Lonlay, Pascale
AU - Hoffmann, Georg F.
AU - Garcia-Cazorla, Angeles
AU - Nagamani, Sandesh C.S.
AU - Baumgartner, Matthias R.
AU - Schulze, Andreas
AU - Dobbelaere, Dries
AU - Yudkoff, Marc
AU - Kölker, Stefan
AU - Zielonka, Matthias
AU - Ah Mew, Nicholas
AU - Berry, Susan A.
AU - McCandless, Shawn E.
AU - Coughlin, Curtis
AU - Enns, Gregory
AU - Gallagher, Renata C.
AU - Burrage, Lindsay C.
AU - Seminara, Jennifer
AU - Harding, Cary O.
AU - Burgard, Peter
AU - Le Mons, Cynthia
AU - Merritt, J. Lawrence
AU - Stricker, Tamar
AU - Bedoyan, Jirair K.
AU - Berry, Gerard T.
AU - Diaz, George A.
AU - Wong, Derek
AU - Tuchman, Mendel
AU - Waisbren, Susan
AU - Weisfeld-Adams, James D.
AU - Burlina, Alberto B.
AU - Leão Teles, Elisa
AU - Pedrón-Giner, Consuelo
AU - Lund, Allan M.
AU - Dionisi-Vici, Carlo
AU - Williams, Monique
AU - Mütze, Ulrike
AU - Karall, Daniela
AU - Blasco-Alonso, Javier
AU - Couce, Maria L.
AU - Sykut-Cegielska, Jolanta
AU - Augoustides-Savvopoulou, Persephone
AU - Ruiz Gomez, Angeles
AU - Barić, Ivo
AU - Schiff, Manuel
AU - Chien, Yin Hsiu
N1 - Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs.
AB - Low protein diet and sodium or glycerol phenylbutyrate, two pillars of recommended long-term therapy of individuals with urea cycle disorders (UCDs), involve the risk of iatrogenic growth failure. Limited evidence-based studies hamper our knowledge on the long-term effects of the proposed medical management in individuals with UCDs. We studied the impact of medical management on growth and weight development in 307 individuals longitudinally followed by the Urea Cycle Disorders Consortium (UCDC) and the European registry and network for Intoxication type Metabolic Diseases (E-IMD). Intrauterine growth of all investigated UCDs and postnatal linear growth of asymptomatic individuals remained unaffected. Symptomatic individuals were at risk of progressive growth retardation independent from the underlying disease and the degree of natural protein restriction. Growth impairment was determined by disease severity and associated with reduced or borderline plasma branched-chain amino acid (BCAA) concentrations. Liver transplantation appeared to have a beneficial effect on growth. Weight development remained unaffected both in asymptomatic and symptomatic individuals. Progressive growth impairment depends on disease severity and plasma BCAA concentrations, but cannot be predicted by the amount of natural protein intake alone. Future clinical trials are necessary to evaluate whether supplementation with BCAAs might improve growth in UCDs.
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U2 - 10.1038/s41598-020-67496-3
DO - 10.1038/s41598-020-67496-3
M3 - Article
C2 - 32686765
AN - SCOPUS:85088256000
SN - 2045-2322
VL - 10
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 11948
ER -