Reference : Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial d...
Scientific journals : Article
Life sciences : Genetics & genetic processes
Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases.
DEBRAY, François-Guillaume mailto [Université de Liège - ULiège > Services généraux (Faculté de médecine vétérinaire) > Service administratif de la Faculté (Médecine vétérinaire)]
Lambert, Marie [> > > >]
Chevalier, Isabelle [> > > >]
Robitaille, Yves [> > > >]
Decarie, Jean-Claude [> > > >]
Shoubridge, Eric A [> > > >]
Robinson, Brian H [> > > >]
Mitchell, Grant A [> >]
American Academy of Pediatrics
Yes (verified by ORBi)
Elk Grove Village
[en] Cause of Death ; Child ; Child, Preschool ; Cohort Studies ; DNA Fragmentation ; DNA, Mitochondrial/genetics ; Female ; Follow-Up Studies ; Humans ; Infant ; Infant, Newborn ; MELAS Syndrome/diagnosis/mortality/therapy ; Male ; Mitochondrial Diseases/diagnosis/genetics/mortality ; Mitochondrial Encephalomyopathies/diagnosis/mortality/therapy ; Mitochondrial Myopathies/diagnosis/genetics/mortality ; Optic Atrophy, Hereditary, Leber/diagnosis/genetics/mortality ; Probability ; Proportional Hazards Models ; Retrospective Studies ; Severity of Illness Index ; Survival Analysis ; Time Factors
[en] 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.

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