Unusual clinical presentations in four cases of Leigh disease, cytochrome C oxidase deficiency, and SURF1 gene mutations
Female; Humans; infant; Male; Phenotype; infant; Q3 Literature Search; Newborn; DNA Mutational Analysis; Muscle; Skeletal/pathology; Proteins/genetics; Frameshift Mutation; Cytochrome-c Oxidase Deficiency/complications/genetics/pathology; Kidney Diseases/etiology; Leigh Disease/complications/genetics/pathology; Membrane Proteins; Mitochondrial Proteins
Mutations in the SURF1 gene are the most frequent causes of Leigh disease with cytochrome c oxidase deficiency. We describe four children with novel SURF1 mutations and unusual features: three had prominent renal symptoms and one had ragged red fibers in the muscle biopsy. We identified five pathogenic mutations in SURF1: two mutations were novel, an in-frame nonsense mutation (834G-->A) and an out-of-frame duplication (820-824dupTACAT). Although renal manifestations have not been described in association with SURF1 mutations, they can be part of the clinical presentation. Likewise, mitochondrial proliferation in muscle (with ragged red fibers) is most unusual in Leigh disease but might be part of an emerging phenotype.
2005
Tay SK; Sacconi S; Akman HO; Morales JF; Morales A; De Vivo DC; Shanske S; Bonilla E; DiMauro S
Journal Of Child Neurology
2005
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/10.1177/08830738050200080701" target="_blank" rel="noreferrer">10.1177/08830738050200080701</a>
Clinical phenotype, prognosis and mitochondrial DNA mutation load in mitochondrial encephalomyopathies
Child; Female; Humans; Male; Adult; Prognosis; Mutation; adolescent; Q3 Literature Search; DNA; Muscle; Mitochondrial Encephalomyopathies/diagnosis/etiology/genetics; Mitochondrial/genetics; Skeletal/pathology
We studied 42 individuals, including 8 patients with either complete or partial syndrome of mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), 8 patients with either complete or partial syndrome of myoclonic epilepsy with ragged-red fibers (MERRF) and 26 maternal family members who carried either the A3243G or A8344G mutation of mitochondrial DNA (mtDNA). Clinical manifestations and prognosis were followed up in the patients harboring the A3243G or A8344G mutation. The relationship between clinical features and proportions of mutant mtDNAs in muscle biopsies, blood cells and/or hair follicles was studied. In the 8 regularly followed patients with the A3243G mutation, 4 died within 1 month to 7 years due to status epilepticus and/or recurrent stroke-like episodes. Two patients developed marked mental deterioration and 2 remained stationary. All of the patients harboring the A8344G mutation were stable or deteriorated slightly, except for 1 patient who died due to brain herniation after putaminal hemorrhage. The A3243G and A8344G mtDNA mutations were heteroplasmic in the muscle biopsies, blood cells and hair follicles of both the probands and their maternal family members. The mean proportion of A3243G mutant mtDNA in the muscle biopsies of the patients with MELAS syndrome (68.5 +/- 21.3%, range 33-92%) was significantly higher than that of the asymptomatic family members (37.1 +/- 12.6%, range 0-51%). The average proportions of A8344G mutant mtDNA in the muscle biopsies (90.1 +/- 3.9%, range 89-95%) and hair follicles (93.9 +/- 6.4%, range 84-99%) of the patients with MERRF syndrome were also significantly higher than those of the asymptomatic family members (muscle: 40.3 +/- 39.5%, range 1-80%; hair follicles: 51.0 +/- 44.5%, range 0.1-82%). We concluded that measurement of the proportion of mutant mtDNA in muscle biopsies may provide useful information in the identification of symptomatic patients with mitochondrial encephalomyopathies. For patients with the A3243G mutation, the prognosis was related to status epilepticus and the number of recurrent stroke-like episodes and was much worse than for patients with the A8344G mutation of mtDNA, who had stable or slowly deteriorating clinical courses.
2002
Huang CC; Kuo HC; Chu CC; Liou CW; Ma YS; Wei YH
Journal Of Biomedical Science
2002
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/10.1007/bf02254979" target="_blank" rel="noreferrer">10.1007/bf02254979</a>
Understanding and managing cancer cachexia
Humans; Neoplasms/complications; Nutritional Failure; Muscle; Skeletal/pathology; Cachexia/etiology/pathology/prevention & control
2003
MacDonald N; Easson AM; Mazurak VC; Dunn GP; Baracos VE
Journal Of The American College Of Surgeons
2003
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/10.1016/s1072-7515(03)00382-x" target="_blank" rel="noreferrer">10.1016/s1072-7515(03)00382-x</a>