Published online April 2, 2007
PEDIATRICS Vol. 119 No. 4 April 2007, pp. 722-733 (doi:10.1542/peds.2006-1866)
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow P3Rs: Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when P3Rs are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow E-mail this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My File Cabinet
Right arrow Download to citation manager
Right arrow reprints & permissions
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via ISI Web of Science (3)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Debray, F.-G.
Right arrow Articles by Mitchell, G. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Debray, F.-G.
Right arrow Articles by Mitchell, G. A.
Related Collections
Right arrow Nutrition & Metabolism

ARTICLE

Long-term Outcome and Clinical Spectrum of 73 Pediatric Patients With Mitochondrial Diseases

François-Guillaume Debray, MDa, Marie Lambert, MDa, Isabelle Chevalier, MDb, Yves Robitaille, MDc, Jean-Claude Decarie, MDd, Eric A. Shoubridge, PhDe, Brian H. Robinson, PhDf and Grant A. Mitchell, MDa

a Divisions of Medical Genetics
b Pediatrics, Department of Pediatrics
c Departments of Pathology
d Medical Imaging, Centre Hospitalier Universitaire Sainte-Justine, Université de Montreal, Montreal, Quebec, Canada
e Department of Human Genetics, Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada
f Metabolism Research Program, Research Institute, Departments of Pediatrics and Biochemistry, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

OBJECTIVES. We sought to determine the clinical spectrum, survival, and long-term functional outcome of a cohort of pediatric patients with mitochondrial diseases and to identify prognostic factors.

METHODS. Medical charts were reviewed for 73 children diagnosed between 1985 and 2005. The functional status of living patients was assessed prospectively by using the standardized Functional Independence Measure scales.

RESULTS. Patients fell into 7 phenotypic categories: neonatal-onset lactic acidosis (10%), Leigh syndrome (18%), nonspecific encephalopathy (32%), mitochondrial (encephalo)myopathy (19%), intermittent neurologic (5%), visceral (11%), and Leber hereditary optic neuropathy (5%). Age at first symptoms ranged from prenatal to 16 years (median: 7 months). Neurologic symptoms were the most common (90%). Visceral involvement was observed in 29% of the patients. A biochemical or molecular diagnosis was identified for 81% of the patients as follows: deficiency of complex IV (27%), of pyruvate dehydrogenase or complex I (25% each), of multiple complexes (13%), and of pyruvate carboxylase (5%) or complexes II+III (5%). A mitochondrial DNA mutation was found in 20% of patients. At present, 46% of patients have died (median age: 13 months), 80% of whom were <3 years of age. Multivariate analysis showed that age at first symptoms was a major independent predictor of mortality: patients with first symptoms before 6 months had a highly increased risk of mortality. Cardiac or visceral involvement and neurologic crises were not independent prognostic factors. Living patients showed a wide range of independence levels that correlated positively with age at first symptoms. Among patients aged >5 years (n = 32), 62% had Functional Independence Measure quotients of >0.75.

CONCLUSIONS. Mitochondrial diseases in children span a wide range of symptoms and severities. Age at first symptoms is the strongest predictor mortality. Despite a high mortality rate in the cohort, 62% of patients aged >5 years have only mild impairment or normal functional outcome.

Key Words: mitochondrial diseases • long-term outcome • functional status

Abbreviations: MD—mitochondrial disease • CSF—cerebrospinal fluid • RRF—ragged red fibers • MELAS—mitochondrial encephalo(myopathy) with lactic acidosis and stroke-like episodes • LHON—Leber hereditary optic neuropathy • PDH—pyruvate dehydrogenase • mtDNA—mitochondrial DNA • NARP— neurogenic weakness–ataxia and retinitis pigmentosa • FIM—Functional Independence Measure • WeeFIM—Functional Independence Measure for Children • CI—confidence interval

Accepted Nov 28, 2006.




This article has been cited by other articles:


Home page
 NEJMHome page
K. J. Staley, K. B. Sims, P. E. Grant, and E. T. Hedley-Whyte
Case 28-2008 -- An 8-Day-Old Infant with Congenital Deafness, Lethargy, and Hypothermia
N. Engl. J. Med., September 11, 2008; 359(11): 1156 - 1167.
[Full Text] [PDF]