Notorious variability in the presentation of mitochondrial disease in the infant and young child complicates its clinical diagnosis. Mitochondrial disease is not a single entity but, rather, a heterogeneous group of disorders characterized by impaired energy production due to genetically based oxidative phosphorylation dysfunction. Together, these disorders constitute the most common neurometabolic disease of childhood with an estimated minimal risk of developing mitochondrial disease of 1 in 5000. Diagnostic difficulty results from not only the variable and often nonspecific presentation of these disorders but also from the absence of a reliable biomarker specific for the screening or diagnosis of mitochondrial disease. A simplified and standardized approach to facilitate the clinical recognition of mitochondrial disease by primary physicians is needed. With this article we aimed to improve the clinical recognition of mitochondrial disease by primary care providers and empower the generalist to initiate appropriate baseline diagnostic testing before determining the need for specialist referral. This is particularly important in light of the international shortage of metabolism specialists to comprehensively evaluate this large and complex disease population. It is hoped that greater familiarity among primary care physicians with the protean manifestations of mitochondrial disease will facilitate the proper diagnosis and management of this growing cohort of pediatric patients who present across all specialties.
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December 2007
State-of-the-Art Review Articles|
December 01 2007
Mitochondrial Disease: A Practical Approach for Primary Care Physicians
Richard H. Haas, MB, BChir, MRCP;
Richard H. Haas, MB, BChir, MRCP
aDepartments of Neurosciences and Pediatrics, University of California San Diego, La Jolla, California
bDepartments of Neurosciences and Pediatrics, Rady Children's Hospital and Health Center, San Diego, California
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Sumit Parikh, MD;
Sumit Parikh, MD
cDivision of Neuroscience, Cleveland Clinic, Cleveland, Ohio
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Marni J. Falk, MD;
Marni J. Falk, MD
dDivision of Human Genetics, Children's Hospital of Philadelphia and University of Pennsylvania, Philadelphia, Pennsylvania
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Russell P. Saneto, DO, PhD;
Russell P. Saneto, DO, PhD
eDivision of Pediatric Neurology, Children's Hospital and Regional Medical Center, University of Washington, Seattle, Washington
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Nicole I. Wolf, MD;
Nicole I. Wolf, MD
fDivision of Child Neurology, University Children's Hospital, Heidelberg, Germany
gDivision of Child Neurology, University Children's Hospital, Zürich, Switzerland
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Niklas Darin, MD;
Niklas Darin, MD
hDivision of Child Neurology, Queen Silvia Children's Hospital, Göteborg, Sweden
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Bruce H. Cohen, MD
Bruce H. Cohen, MD
cDivision of Neuroscience, Cleveland Clinic, Cleveland, Ohio
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Address correspondence to Richard H. Haas, MB, BChir, MRCP, Departments of Neurosciences and Pediatrics, University of California San Diego, 9500 Gilman Dr, La Jolla, CA 92093-0935. E-mail: rhaas@ucsd.edu
Pediatrics (2007) 120 (6): 1326–1333.
Article history
Accepted:
September 19 2007
Citation
Richard H. Haas, Sumit Parikh, Marni J. Falk, Russell P. Saneto, Nicole I. Wolf, Niklas Darin, Bruce H. Cohen; Mitochondrial Disease: A Practical Approach for Primary Care Physicians. Pediatrics December 2007; 120 (6): 1326–1333. 10.1542/peds.2007-0391
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Comments
Mitochondrial pathology
Besides the classical aspects of clinical pathology in mitochondrial energy metabolism so elegantly reviewed in this work, it may be interesting to regard the additional roles of succinate dehydrogenase (SDH) at the complex II of the respiratory chain. Its activity can be inhibited by toxicants, like malonic acid, 3-nitropropionic acid or alkoxyacetic acids (1) which leads to deranged electron flow in the respiratory chain. Accumulating succinate also inhibits the inactivation of hypoxia inducible factor by the proteasome. Acquired and inherited diminution of SDH has an important role e.g. in the epigenetic malignant transformation (2). Thus, mitochondria have central roles also in other acute and chronic diseases in addition to the classical neuromuscular syndromes.
1 Liesivuori J, Laitinen J, Savolainen H. 1999. Rat model for renal effects of 2-alkoxyalcohols and their acetates. Arch Toxicol 73: 229-232.
2 Baysal BE. A recurrent stop-codon mutation in succinate dehydrogenases B gene in normal peripheral blood and childhood T-cell acute leukemia. 2007. Plos ONE 2: e436.
Conflict of Interest:
None declared