Disorders of Leucine, Isoleucine, and Valine Metabolism
Disorders in the catabolic pathways of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine encompass diverse organic and aminoacidurias. Clinical severity may range from asymptomatic findings in some to life-threatening episodes and mult
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Disorders of Leucine, Isoleucine, and Valine Metabolism Ina Knerr, Jerry Vockley, and K. Michael Gibson
Contents
Summary
7.1
Introduction......................................................................
103
7.2
Nomenclature ...................................................................
106
7.3
Metabolic Pathway ..........................................................
107
7.4
Signs and Symptoms ........................................................
107
7.5
Reference Values ..............................................................
122
7.6
Pathological Values ..........................................................
124
7.7
Diagnostic Flow Chart.....................................................
127
Specimen Collection, Prenatal Diagnosis, and DNA Analysis ............................................................ 7.8.1 Specimen Collection .......................................................... 7.8.2 Prenatal Diagnosis ............................................................. 7.8.3 DNA Analysis ....................................................................
128 128 128 129
7.9
Treatment Summary........................................................
130
References ....................................................................................
140
7.8
Disorders in the catabolic pathways of the branched-chain amino acids (BCAA) leucine, isoleucine, and valine encompass diverse organic and aminoacidurias. Clinical severity may range from asymptomatic findings in some to lifethreatening episodes and multiorgan involvement in others. Several of these defects reflect a complex pathogenesis related to mitochondrial dysfunction, particularly the 3-methylglutaconic acidurias. As a general rule, treatment includes the following: (1) dietary restriction of the precursor BCAA along with optimal nutritional supply, (2) adjunct therapy (e.g., with L-carnitine, appropriate cofactors, other conjugating compounds), (3) rapid intervention for metabolic decompensation. Late complications of these diseases must be anticipated, such as liver and renal failure. In asymptomatic individuals, instructions regarding risks for metabolic stress and fasting avoidance, along with clinical monitoring, represent appropriate prophylactic interventions at this time.
7.1
I. Knerr (*) National Centre for Inherited Metabolic Disorders, Children’s University Hospital, Temple Street, Dublin 1, Ireland e-mail: [email protected] J. Vockley Department of Pediatrics, Children’s Hospital of Pittsburgh, University of Pittsburgh Medical Center, University of Pittsburgh, 4401 Penn Avenue, Pittsburgh, PA 15224, USA e-mail: [email protected] K.M. Gibson Section of Clinical Pharmacology, Washington State University, SAC 525M, 412 E. Spokane Falls Blvd, Spokane, WA 99202-2131, USA e-mail: [email protected]
Introduction
The catabolic pathways of branched-chain amino acids (BCAA), namely, leucine, isoleucine, and valine, consist of multiple steps including transamination, oxidative decarboxyla
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