Long-term outcome and clinical spectrum of 73 pediatric patients with mitochondrial diseases
Child; Female; Humans; infant; Male; Cohort Studies; Follow-Up Studies; Severity of Illness Index; Survival Analysis; Longitudinal Studies; Probability; Time Factors; Proportional Hazards Models; Preschool; infant; Q3 Literature Search; Newborn; AIM; IM; retrospective studies; cause of death; DNA; Mitochondrial Diseases/ge [Genetics]; Mitochondrial/ge [Genetics]; MELAS Syndrome/di [Diagnosis]; Mitochondrial Encephalomyopathies/di [Diagnosis]; DNA Fragmentation; HEREDITARY; Leber/di [Diagnosis]; Leber/ge [Genetics]; Leber/mo [Mortality]; MELAS Syndrome/mo [Mortality]; MELAS Syndrome/th [Therapy]; Mitochondrial Diseases/di [Diagnosis]; Mitochondrial Diseases/mo [Mortality]; Mitochondrial Encephalomyopathies/mo [Mortality]; Mitochondrial Encephalomyopathies/th [Therapy]; Mitochondrial Myopathies/di [Diagnosis]; Mitochondrial Myopathies/ge [Genetics]; Mitochondrial Myopathies/mo [Mortality]; Optic Atrophy
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 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.
2007
Debray FG; Lambert M; Chevalier I; Robitaille Y; Decarie JC; Shoubridge EA; Robinson BH; Mitchell GA
Pediatrics
2007
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1542/peds.2006-1866" target="_blank" rel="noreferrer">10.1542/peds.2006-1866</a>
Progressive sensorineural hearing loss in children with mitochondrial encephalomyopathies
Child; Female; Humans; Male; Adult; Hearing Loss; Longitudinal Studies; Speech; adolescent; Preschool; IM; Auditory; Evoked Potentials; Acoustic Impedance Tests; Acoustic/ph [Physiology]; Audiometry; Brain Stem/ph [Physiology]; Friedreich Ataxia/di [Diagnosis]; Friedreich Ataxia/pp [Physiopathology]; Kearns-Sayer Syndrome/di [Diagnosis]; Kearns-Sayer Syndrome/pp [Physiopathology]; MELAS Syndrome/di [Diagnosis]; MELAS Syndrome/pp [Physiopathology]; Mitochondrial Encephalomyopathies/di [Diagnosis]; Mitochondrial Encephalomyopathies/pp [Physiopathology]; Otoacoustic Emissions; Pure-Tone; Reflex; Sensorineural/di [Diagnosis]; Sensorineural/pp [Physiopathology]; Spontaneous/ph [Physiology]
OBJECTIVE: Mitochondrial disorders are responsible for a variety of neurological syndromes. Specific mitochondrial DNA mutations have been identified recently in some of these rare disorders. Clinical symptoms may occur in different organs to various extent; often they are associated with progressive hearing loss. The aims of this study were to determine incidence, onset, and characteristics of hearing loss in children with mitochondrial encephalomyopathies and to investigate a possible correlation between the degree of hearing loss and neurological symptoms. In addition, we investigated the prognostic value of hearing loss as a predictor of the disease. STUDY DESIGN: From August 1992 to September 1998, 29 patients ranging in age from 5 to 23 years (mean years) were studied. These children were hospitalized for diagnostic purposes in the neuropediatric department. METHODS: The mitochondrial disorder was diagnosed by clinical and laboratory testings, including analysis of the mtDNA. Audiological evaluation consisted of measurements of pure-tone and speech audiometry, tympanometry, and acoustic refle- threshold testing, auditory brainstem response, and evoked as well as distortion-product otoacoustic emissions. RESULTS: A sensorineural hearing loss was identified in 12 children. Three of these were diagnosed as having classic Kearns-Sayre syndrome; five as having multisystem KSS; two as having the syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS); one as having KSS-MELAS overlap syndrome; and one as having Friedreich ataxia. Longitudinal testing was performed in seven children, and in all of them a progression of the hearing loss could be demonstrated. Audiological test results in all 12 children suggested cochlear as well as retrocochlear origin of the hearing loss presenting independently from the severity of hearing impairment. No correlation between the characteristics and degrees of hearing loss and the number and severity of clinical neurological symptoms could be found. CONCLUSIONS: The present study demonstrated a high incidence (42%) of sensorineural hearing loss in children with mitochondrial encephalomyopathies. The progressive nature of the hearing impairment was confirmed by a significant correlation between the duration in years and severity of hearing loss in the children. The hearing loss does not have a prognostic value for the progression of the disorder. Based on our findings, we recommend regular audiometric examinations in patients with mitochondrial disorders.
2001
Zwirner P; Wilichowski E
Laryngoscope
2001
Article information provided for research and reference use only. PedPalASCNET does not hold any rights over the resource listed here. All rights are retained by the journal listed under publisher and/or the creator(s).
Journal Article
<a href="http://doi.org/10.1097/00005537-200103000-00024" target="_blank" rel="noreferrer">10.1097/00005537-200103000-00024</a>