Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases.
OBJECTIVE
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.
Debray
François-Guillaume
FG
Medical Genetics Division, Centre Hospitalier Universitaire Sainte-Justine, Université de Montreal, Montreal, Quebec, Canada H3T 1C5.
Lambert
Marie
M
Chevalier
Isabelle
I
Robitaille
Yves
Y
Decarie
Jean-Claude
JC
Shoubridge
Eric A
EA
Robinson
Brian H
BH
Mitchell
Grant A
GA
D002423:Cause of Death; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D053938:DNA Fragmentation; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D017241:MELAS Syndrome / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D008297:Male; D028361:Mitochondrial Diseases / Q000175:diagnosis* / Q000235:genetics / Q000401:mortality*; D017237:Mitochondrial Encephalomyopathies / Q000175:diagnosis / Q000401:mortality / Q000628:therapy; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D029242:Optic Atrophy, Hereditary, Leber / Q000175:diagnosis / Q000235:genetics / Q000401:mortality; D011336:Probability; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012720:Severity of Illness Index; D016019:Survival Analysis; D013997:Time Factors
D004272:DNA, Mitochondrial