Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment

Molema, Femke; Gleich, Florian; Burgard, Peter; Ploeg, Ans T. van der; Summar, Marshall; Chapman, Kimberly A.; Lund, Allan M.; Rizopoulos, Dimitris; Kölker, Stefan; Williams, Monique; Hörster, Friederike; Jelsig, Anne Marie; Lonlay, Pascale de; Wijburg, Frits A.; Bosch, Annet M.; Freisinger, Peter; Posset, Roland; Augoustides‐Savvopoulou, Persephone; Avram, Paula; Deleanu, Călin; Baumgartner, Matthias R.; Häberle, Johannes; Blasco‐Alonso, Javier; Burlina, Alberto; Rubert, Laura; Cazorla, Angeles Garcia; Saladelafont, Elisenda Cortès i; Dionisi‐Vici, Carlo; Martinelli, Diego; Dobbelaere, Dries; Mention, Karine; Grünewald, Stéphanie; Chakrapani, Anupam; Hwu, Wuh‐Liang; Chien, Yin‐Hsiu; Lee, Ni‐Chung; Karall, Daniela; Scholl‐Bürgi, Sabine; Laet, Corinne De; Matsumoto, Shirou; Meırleır, Linda De; Schiff, Manuel; Quintana, Luis Peña; Djordjević, Milan; Sarajlija, Adrijan; Sykut-Cegielska, Jolanta; Wiśniewska, Anita; Leão‐Teles, Elisa; Alves, Susana P.; Vara, Roshni; Vives-Piñera, Inmaculada; Gil-Ortega, David; Morris, Andrew A. M.; Zeman, Jiří; Honzík, Tomáš; Chabrol, B.; Arnaudo, F.; Cano, Aline; Thompson, NP; Eyskens, François; Lindner, Martin; Lüsebrink, Natalia; Jalan, Anil; Sokal, Étienne; Legros, Vincent; Nassogne, Marie‐Cécile; Barić, Ivo

doi:10.1016/j.ymgme.2019.02.003

Cited by 28 publications

(25 citation statements)

References 57 publications

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“…In line, height z-scores in UCD patients were positively associated with patient's plasma L-leucine (CPS1-D, mOTC-D and HHH-syndrome) and L-valine (ASS1-D and ASL-D) concentrations 14 , clearly supporting our findings. However, while the latter observation was based on a cross-sectional analysis, our results further substantiate the relevance of the identified association between BCAA depletion and growth failure by providing longitudinal data in UCDs.…”

Section: Discussionsupporting

confidence: 89%

“…In contrast, symptomatic individuals of any UCD studied receiving conservative management, particularly EO individuals, showed progressive growth impairment over time, which is in line with previous studies 14 , 15 , highlighting that disease severity rather than the type of UCD is a major determinant of linear growth. Since treatment intensity was shown to reflect disease severity and protein restriction has been hypothesized to be causally related to growth failure in UCDs 12 , we further investigated the impact of current treatment modalities on linear growth, particularly with regard to natural protein intake as underlying cause of potential growth retardation.…”

Section: Discussionsupporting

confidence: 89%

“…However, while the latter observation was based on a cross-sectional analysis, our results further substantiate the relevance of the identified association between BCAA depletion and growth failure by providing longitudinal data in UCDs. Of note, plasma BCAA concentrations were within the lower normal range or reduced in UCD individuals in our study, independent from the administration of EAA supplements, which has already been reported by Molema et al 14 , indicating that the current clinical practice of prescribing EAA or BCAA supplements is not sufficiently compensating for BCAA depletion in UCD individuals. Since LTx appeared to be beneficial for the cognitive outcome in UCD individuals in a cross-sectional analysis 12 , 14 , we further investigated the impact of LTx on linear growth.…”

Section: Discussionsupporting

confidence: 78%

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Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Posset

Garbade

Gleich

et al. 2020

Sci Rep

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Urea Cycle Disorders Consortium (UCDC) * & European registry and network for Intoxication type Metabolic Diseases (E-IMD) * 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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Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 89%

Section: Discussionsupporting

confidence: 78%

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Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Posset

Garbade

Gleich

et al. 2020

Sci Rep

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“…The same group also described the comparison of metabolite concentrations for control populations from two different geographical regions [13]. We also published metabolite concentrations for normal and diabetes groups from Eastern Europe (Bucharest), and we discussed the results in comparison with previously published data [14,15]-our interests covering diagnoses of various metabolic disorders [16][17][18][19].…”

Section: Introductionmentioning

confidence: 98%

“…Moreover, some completely asymptomatic MMA cases have been also reported [29,30]. The effects of MMA vary from mild to life-threatening and its treatment is complex, requiring regular monitoring and frequent therapeutic and dietary adjustments [19].…”

Section: Introductionmentioning

confidence: 99%

Monitoring Methylmalonic Aciduria by NMR Urinomics

Nicolescu

Daniela²,

Boiciuc³

et al. 2020

Molecules

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The paper reports on monitoring methylmalonic aciduria (MMA)-specific and non-specific metabolites via NMR urinomics. Five patients have been monitored over periods of time; things involved were diet, medication and occasional episodes of failing to comply with prescribed diets. An extended dataset of targeted metabolites is presented, and correlations with the type of MMA are underlined. A survey of previous NMR studies on MMA is also presented.

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Dietary management and growth outcomes in children with propionic acidemia: A natural history study

et al. 2021

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Background Propionic acidemia (PROP) is an autosomal recessive inherited deficiency of propionyl‐CoA carboxylase (PCC) which is involved in the catalytic breakdown of the amino acids valine, isoleucine, methionine, and threonine. PROP nutritional management is based on dietary protein restriction and use of special medical formulas which are free of the offending amino acids, but are enriched in leucine. The resulting imbalance among branched‐chain amino acids negatively impacts plasma concentrations of valine and isoleucine, which might impact growth in children with PROP. Objective and Methods Our primary objective was to describe dietary protein and calorie intake and their impact on long‐term growth outcomes of four PROP patients. This was accomplished through a longitudinal retrospective chart review following the cohort from birth to 18 years. Results All children (n = 4) had poor growth outcomes with persistently reduced height‐for‐age Z scores, and elevated weight and body mass index (BMI) Z scores. Energy intakes for all subjects were within 80% to 120% of the dietary reference intakes for age. All children had low intakes of intact protein compared with current guidelines and were supplemented with medical formula and single l‐amino acids (valine and/or isoleucine), which led to the excess consumption of total protein. Conclusion Despite adequate total protein and energy intakes, all children had persistently low height Z scores. Restricted intact protein consumption together with the abundant use of medical formula could have affected overall growth. To optimize dietary management in patients with PROP, further research is needed to determine the optimal intake of medical formula relative to intact protein.

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Decreased plasma l-arginine levels in organic acidurias (MMA and PA) and decreased plasma branched-chain amino acid levels in urea cycle disorders as a potential cause of growth retardation: Options for treatment

Cited by 28 publications

References 57 publications

Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Long-term effects of medical management on growth and weight in individuals with urea cycle disorders

Monitoring Methylmalonic Aciduria by NMR Urinomics

Dietary management and growth outcomes in children with propionic acidemia: A natural history study

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