Skip header and navigation

Refine By

10 records – page 1 of 1.

Alaskan Husky encephalopathy--a canine neurodegenerative disorder resembling subacute necrotizing encephalomyelopathy (Leigh syndrome).

https://arctichealth.org/en/permalink/ahliterature6759
Source
Acta Neuropathol (Berl). 2000 Jul;100(1):50-62
Publication Type
Article
Date
Jul-2000
Author
O. Brenner
J J Wakshlag
B A Summers
A. de Lahunta
Author Affiliation
Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853-6401, USA.
Source
Acta Neuropathol (Berl). 2000 Jul;100(1):50-62
Date
Jul-2000
Language
English
Publication Type
Article
Keywords
Age Factors
Age of Onset
Alaska
Animals
Brain - pathology - physiopathology
Central Nervous System - pathology - physiopathology
Disease Progression
Dog Diseases - pathology - physiopathology
Dogs
Female
Inbreeding
Leigh Disease - veterinary
Male
Research Support, Non-U.S. Gov't
Spinal Cord - pathology - physiopathology
Abstract
The gross and histopathological findings in the brain and spinal cord of five Alaskan Husky dogs with a novel incapacitating and ultimately fatal familial and presumed hereditary neurodegenerative disorder are described. Four dogs presented with neurological deficits before the age of 1 year (7-11 months) and one animal at 2.5 years old. Clinical signs in all dogs were of acute onset and included ataxia, seizures, behavioral abnormalities, blindness, facial hypalgesia and difficulties in prehension of food. In animals allowed to survive, the disease was static but with frequent recurrences. Pathological findings were limited to the central nervous system. Grossly visible bilateral and symmetrical cavitated foci were consistently present in the thalamus with variable extension into the caudal brain stem. Microscopic lesions were more widespread and included foci of bilateral and symmetrical degeneration in the basal nuclei, midbrain, pons and medulla, as well as multifocal lesions at the base of sulci in the cerebral cortex and in the gray matter of cerebellar folia in the ventral vermis. Neuronal loss with concomitant neuronal sparing, spongiosis, vascular hypertrophy and hyperplasia, gliosis, cavitation and transient mixed inflammatory infiltration were the main histopathological findings. In addition, a population of reactive gemistocytic astrocytes with prominent cytoplasmic vacuolation was noted in the thalamus. Lesions of this nature in this distribution within the neuroaxis have not been reported in dogs. The neuropathological findings resemble Leigh's disease/subacute necrotizing encephalomyelopathy of man. Neuronal sparing in conjunction with apparently transient astrocytic vacuolation point to the possible pathogenetic role of astrocytes in the evolution of these lesions. An inherited metabolic derangement of unknown nature is postulated as the cause of this breed-specific disorder.
PubMed ID
10912920 View in PubMed
Less detail

A biochemically distinct form of cytochrome oxidase (COX) deficiency in the Saguenay-Lac-Saint-Jean region of Quebec.

https://arctichealth.org/en/permalink/ahliterature220557
Source
Am J Hum Genet. 1993 Aug;53(2):481-7
Publication Type
Article
Date
Aug-1993
Author
F. Merante
R. Petrova-Benedict
N. MacKay
G. Mitchell
M. Lambert
C. Morin
M. De Braekeleer
R. Laframboise
R. Gagné
B H Robinson
Author Affiliation
Research Institute, Hospital for Sick Children, Toronto, Ontario, Canada.
Source
Am J Hum Genet. 1993 Aug;53(2):481-7
Date
Aug-1993
Language
English
Publication Type
Article
Keywords
Acidosis, Lactic - enzymology
Amniocentesis
Brain Chemistry
Child, Preschool
Cytochrome-c Oxidase Deficiency
DNA - analysis
DNA, Mitochondrial - analysis
Electron Transport Complex IV - genetics
Fatty Liver - enzymology
Fibroblasts - enzymology
France - ethnology
Humans
Immunoblotting
Infant
Infant, Newborn
Leigh Disease - enzymology - genetics
Liver - enzymology
Organ Specificity
Quebec
RNA, Messenger - analysis
Abstract
We report the results of biochemical and molecular investigations on a group of patients from the Saguenay-Lac-Saint-Jean region of Quebec who have an unusual form of cytochrome oxidase deficiency and Leigh disease. This group can be distinguished from the classical presentation of cytochrome oxidase deficiency with Leigh disease, by the severity of the biochemical defect in different tissues. The activity in skin fibroblasts, amniocytes, and skeletal muscle of cytochrome oxidase is 50% of normal, while in kidney and heart it is close to normal values. Brain and liver, on the other hand, have very low activities. The defect in activity appears to result from a failure of assembly of the cytochrome oxidase complex in liver, but levels of mRNA for both mitochondrially encoded and nuclear-encoded subunits in liver and skin fibroblasts were found to be the same as those in controls. The cDNA sequence of the liver-specific cytochrome oxidase subunits VIa and VIIa were determined in samples from patient liver and skin fibroblasts and showed normal coding sequence.
Notes
Cites: Pediatr Res. 1977 Oct;11(10 Pt 2):1088-93904972
Cites: Am J Hum Genet. 1993 Aug;53(2):488-968392291
Cites: Proc Natl Acad Sci U S A. 1979 Sep;76(9):4350-4388439
Cites: Biochemistry. 1979 Nov 27;18(24):5294-9518835
Cites: Anal Biochem. 1983 Mar;129(2):517-216303162
Cites: Ann Neurol. 1983 Aug;14(2):226-346312869
Cites: Eur J Pediatr. 1984 Jan;141(3):178-806321192
Cites: J Clin Invest. 1984 Sep;74(3):685-976432847
Cites: Biochem Soc Trans. 1985 Aug;13(4):651-32993077
Cites: J Clin Invest. 1986 May;77(5):1422-73009544
Cites: J Pediatr. 1987 Feb;110(2):216-223027293
Cites: Am J Hum Genet. 1987 Oct;41(4):584-932821802
Cites: Ann Neurol. 1987 Oct;22(4):498-5062829705
Cites: FEBS Lett. 1988 Aug 15;236(1):100-42841159
Cites: Nucleic Acids Res. 1989 Aug 11;17(15):64092549515
Cites: Nucleic Acids Res. 1989 Sep 12;17(17):71072550906
Cites: FEBS Lett. 1990 Apr 24;263(2):213-62159420
Cites: J Biol Chem. 1990 Aug 25;265(24):14220-62167310
Cites: EMBO J. 1990 Sep;9(9):2759-642167832
Cites: Pediatr Res. 1990 Nov;28(5):549-552175027
Cites: Neurology. 1991 Apr;41(4):491-81849240
Cites: Am J Hum Genet. 1992 Apr;50(4):852-81550128
Cites: Eur J Pediatr. 1992 May;151(5):347-521327797
Cites: Pediatrics. 1977 Dec;60(6):850-7202917
PubMed ID
8392290 View in PubMed
Less detail

Clinical, metabolic, and genetic aspects of cytochrome C oxidase deficiency in Saguenay-Lac-Saint-Jean.

https://arctichealth.org/en/permalink/ahliterature220556
Source
Am J Hum Genet. 1993 Aug;53(2):488-96
Publication Type
Article
Date
Aug-1993
Author
C. Morin
G. Mitchell
J. Larochelle
M. Lambert
H. Ogier
B H Robinson
M. De Braekeleer
Author Affiliation
Département de Pédiatrie, Hôpital de Chicoutimi, Québec.
Source
Am J Hum Genet. 1993 Aug;53(2):488-96
Date
Aug-1993
Language
English
Publication Type
Article
Keywords
Acidosis, Lactic - enzymology
Child
Child, Preschool
Cytochrome-c Oxidase Deficiency
Fatty Liver - enzymology
Female
France - ethnology
Gene Frequency
Genes, Recessive
Humans
Infant
Leigh Disease - enzymology - genetics - pathology
Male
Mitochondria, Liver - enzymology
Muscle Hypotonia - enzymology
Pedigree
Quebec
Abstract
Thirty-four children with lactic acidosis and Leigh encephalopathy due to cytochrome C oxidase (COX) deficiency distributed in 28 families have recently been identified in northeastern Quebec, particularly in the Saguenay-Lac-Saint-Jean (SLSJ) region. The segregation analysis was consistent with an autosomal recessive mode of inheritance. The incidence was estimated at 1/2,063 live births between 1979 and 1990, and the carrier rate was estimated at 1/23 inhabitants in SLSJ. In SLSJ, the places of origin of the COX-deficient children and their parents did not show a clustered nonuniform distribution. The genealogical reconstruction of 54 obligate carriers identified 26 ancestors common to all of them. Twenty-two were 17th-century Europeans, suggesting that the COX-deficient gene was introduced in the French-Canadian population by early settlers. These results support the hypothesis of a founder effect for COX deficiency in northeastern Quebec. Clinical findings are reported for 15 of these COX-deficient patients, age 6 mo to 11 years. Moderate developmental delay, hypotonia, ataxia, strabismus, and mild facial dysmorphism were frequent. Eleven children died in episodes of fulminant metabolic acidosis. The patients had elevated blood and cerebrospinal fluid lactate levels, decreased blood bicarbonate levels, and normal blood pH. Leigh disease and microvesicular steatosis of the liver were present in all affected patients for whom postmortem examination was performed. This biochemically uniform group of patients showed a wide range of clinical severity.
Notes
Cites: Clin Neurol Neurosurg. 1987;89(4):217-303319345
Cites: J Pediatr. 1987 Oct;111(4):525-333116190
Cites: J Pediatr. 1988 May;112(5):734-92834526
Cites: J Pediatr. 1988 Jul;113(1 Pt 1):156-93290414
Cites: J Inherit Metab Dis. 1988;11 Suppl 2:189-922846961
Cites: J Inherit Metab Dis. 1989;12(3):247-562559245
Cites: J Neurol Sci. 1990 Jan;95(1):63-762159985
Cites: Am J Hum Genet. 1990 Aug;47(2):302-72378355
Cites: Pediatr Res. 1990 Nov;28(5):536-412175026
Cites: Am J Hum Genet. 1992 Apr;50(4):852-81550128
Cites: Am J Hum Genet. 1993 Aug;53(2):481-78392290
Cites: Am J Dis Child. 1991 Jun;145(6):661-41852096
Cites: J Neurol Sci. 1991 Jul;104(1):97-1111655984
Cites: Hum Hered. 1991;41(3):168-731937490
Cites: Pediatrics. 1977 Dec;60(6):850-7202917
Cites: J Inherit Metab Dis. 1983;6(3):121-26321854
Cites: J Inherit Metab Dis. 1983;6(3):127-86422145
Cites: Brain Dev. 1984;6(4):362-726093613
Cites: Biochem Soc Trans. 1985 Aug;13(4):651-32993077
Cites: J Pediatr. 1987 Feb;110(2):216-223027293
Cites: Ann Neurol. 1987 Oct;22(4):498-5062829705
PubMed ID
8392291 View in PubMed
Less detail

Mitochondrial EFTs defects in juvenile-onset Leigh disease, ataxia, neuropathy, and optic atrophy.

https://arctichealth.org/en/permalink/ahliterature258533
Source
Neurology. 2014 Aug 19;83(8):743-51
Publication Type
Article
Date
Aug-19-2014
Author
Sofia Ahola
Pirjo Isohanni
Liliya Euro
Virginia Brilhante
Aarno Palotie
Helena Pihko
Tuula Lönnqvist
Tanita Lehtonen
Jukka Laine
Henna Tyynismaa
Anu Suomalainen
Source
Neurology. 2014 Aug 19;83(8):743-51
Date
Aug-19-2014
Language
English
Publication Type
Article
Keywords
Adolescent
Ataxia - diagnosis - genetics
DNA, Mitochondrial - genetics
Female
Finland
Humans
Leigh Disease - diagnosis - genetics
Mitochondria - genetics
Mutation - genetics
Optic Atrophy - diagnosis - genetics
Pedigree
Peptide Elongation Factors - genetics
Phenotype
Young Adult
Abstract
We report novel defects of mitochondrial translation elongation factor Ts (EFTs), with high carrier frequency in Finland and expand the manifestations of this disease group from infantile cardiomyopathy to juvenile neuropathy/encephalopathy disorders.
DNA analysis, whole-exome analysis, protein biochemistry, and protein modeling.
We used whole-exome sequencing to find the genetic cause of infantile-onset mitochondrial cardiomyopathy, progressing to juvenile-onset Leigh syndrome, neuropathy, and optic atrophy in 2 siblings. We found novel compound heterozygous mutations, c.944G>A [p.C315Y] and c.856C>T [p.Q286X], in the TSFM gene encoding mitochondrial EFTs. The same p.Q286X variant was found as compound heterozygous with a splice site change in a patient from a second family, with juvenile-onset optic atrophy, peripheral neuropathy, and ataxia. Our molecular modeling predicted the coding-region mutations to cause protein instability, which was experimentally confirmed in cultured patient cells, with mitochondrial translation defect and lacking EFTs. Only a single TSFM mutation has been previously described in different populations, leading to an infantile fatal multisystem disorder with cardiomyopathy. Sequence data from 35,000 Finnish population controls indicated that the heterozygous carrier frequency of p.Q286X change was exceptionally high in Finland, 1:80, but no homozygotes were found in the population, in our mitochondrial disease patient collection, or in an intrauterine fetal death material, suggesting early developmental lethality of the homozygotes.
We show that in addition to early-onset cardiomyopathy, TSFM mutations should be considered in childhood and juvenile encephalopathies with optic and/or peripheral neuropathy, ataxia, or Leigh disease.
PubMed ID
25037205 View in PubMed
Less detail

MtDNA mutations are a common cause of severe disease phenotypes in children with Leigh syndrome.

https://arctichealth.org/en/permalink/ahliterature90671
Source
Biochim Biophys Acta. 2009 May;1787(5):484-90
Publication Type
Article
Date
May-2009
Author
Naess Karin
Freyer Christoph
Bruhn Helene
Wibom Rolf
Malm Gunilla
Nennesmo Inger
von Döbeln Ulrika
Larsson Nils-Göran
Author Affiliation
Department of Clinical Sciences, Karolinska University Hospital, S-141 86 Stockholm, Sweden.
Source
Biochim Biophys Acta. 2009 May;1787(5):484-90
Date
May-2009
Language
English
Publication Type
Article
Keywords
Adenosine Triphosphate - metabolism
Child
Child, Preschool
DNA, Mitochondrial - genetics
DNA-Directed DNA Polymerase - genetics
Female
Glutamate Dehydrogenase - genetics
Humans
Infant
Infant, Newborn
Kinetics
Leigh Disease - enzymology - genetics - mortality
Male
Membrane Proteins - genetics
Mitochondrial Diseases - genetics
Mitochondrial Proteins - genetics
Phenotype
Polymorphism, Restriction Fragment Length
Polymorphism, Single Nucleotide
Severity of Illness Index
Survival Analysis
Abstract
Leigh syndrome is a common clinical manifestation in children with mitochondrial disease and other types of inborn errors of metabolism. We characterised clinical symptoms, prognosis, respiratory chain function and performed extensive genetic analysis of 25 Swedish children suffering from Leigh syndrome with the aim to obtain insights into the molecular pathophysiology and to provide a rationale for genetic counselling. We reviewed the clinical history of all patients and used muscle biopsies in order to perform molecular, biochemical and genetic investigations, including sequencing the entire mitochondrial DNA (mtDNA), the mitochondrial DNA polymerase (POLGA) gene and the surfeit locus protein 1 (SURF1) gene. Respiratory chain enzyme activity measurements identified five patients with isolated complex I deficiency and five with combined enzyme deficiencies. No patient presented with isolated complex IV deficiency. Seven patients had a decreased ATP production rate. Extensive sequence analysis identified eight patients with pathogenic mtDNA mutations and one patient with mutations in POLGA. Mutations of mtDNA are a common cause of LS and mtDNA analysis should always be included in the diagnosis of LS patients, whereas SURF1 mutations are not a common cause of LS in Sweden. Unexpectedly, age of onset, clinical symptoms and prognosis did not reveal any clear differences in LS patients with mtDNA or nuclear DNA mutations.
PubMed ID
19103152 View in PubMed
Less detail

A multicenter study on Leigh syndrome: disease course and predictors of survival.

https://arctichealth.org/en/permalink/ahliterature256766
Source
Orphanet J Rare Dis. 2014;9:52
Publication Type
Article
Date
2014
Author
Kalliopi Sofou
Irenaeus F M De Coo
Pirjo Isohanni
Elsebet Ostergaard
Karin Naess
Linda De Meirleir
Charalampos Tzoulis
Johanna Uusimaa
Isabell B De Angst
Tuula Lönnqvist
Helena Pihko
Katariina Mankinen
Laurence A Bindoff
Már Tulinius
Niklas Darin
Author Affiliation
Department of Paediatrics, University of Gothenburg, The Queen Silvia's Children Hospital, SE-416 85 Gothenburg, Sweden. kalliopi.sofou@vgregion.se.
Source
Orphanet J Rare Dis. 2014;9:52
Date
2014
Language
English
Publication Type
Article
Keywords
Adolescent
Adult
Child
Child, Preschool
Female
Humans
Leigh Disease - mortality - pathology
Male
Prognosis
Retrospective Studies
Young Adult
Abstract
Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients.
This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu.
A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival.
This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel predictors of disease severity and long-term prognosis.
Notes
Cites: Brain. 1971;94(1):1-305552162
Cites: Ann Neurol. 1993 Jun;33(6):652-58498846
Cites: Ann Neurol. 1996 Mar;39(3):343-518602753
Cites: Am J Hum Genet. 1998 Dec;63(6):1594-79837811
Cites: J Neurol Neurosurg Psychiatry. 1951 Aug;14(3):216-2114874135
Cites: Pediatr Neurol. 2005 May;32(5):334-4015866434
Cites: Chin Med J (Engl). 2006 Mar 5;119(5):373-716542579
Cites: Brain. 2007 Mar;130(Pt 3):853-6117287286
Cites: Mitochondrion. 2007 Jul;7(4):241-5217376748
Cites: J Child Neurol. 2007 Oct;22(10):1222-617940250
Cites: Mitochondrion. 2008 Dec;8(5-6):396-41318590986
Cites: Pediatr Neurol. 2009 Feb;40(2):88-9319135620
Cites: Biochim Biophys Acta. 2009 May;1787(5):484-9019103152
Cites: Fetal Diagn Ther. 2009;25(2):177-8219321960
Cites: Pediatr Neurol. 2009 Oct;41(4):309-1119748055
Cites: Mol Genet Metab. 2010 May;100(1):65-7020202874
Cites: Neurology. 2003 Mar 11;60(5):865-812629249
Cites: J Pediatr. 2003 Aug;143(2):208-1212970634
Cites: Epilepsia. 2010 Jun;51(6):1069-7719889013
Cites: Eur Heart J. 2003 Feb;24(3):280-812590906
Cites: Ann Neurol. 2001 Mar;49(3):377-8311261513
Cites: AJNR Am J Neuroradiol. 2000 Sep;21(8):1502-911003287
Cites: Orphanet J Rare Dis. 2013;8:9623829769
Cites: Mitochondrion. 2013 Jul;13(4):364-7123623855
Cites: Neurogenetics. 2013 Feb;14(1):85-723334465
Cites: J Inherit Metab Dis. 2012 Sep;35(5):737-4722644603
Cites: Hum Mutat. 2012 Aug;33(8):1192-20022488715
Cites: J Clin Neurosci. 2012 Feb;19(2):195-20222273117
Cites: J Med Genet. 2011 Mar;48(3):183-921266382
PubMed ID
24731534 View in PubMed
Less detail

SUCLA2 mutations are associated with mild methylmalonic aciduria, Leigh-like encephalomyopathy, dystonia and deafness.

https://arctichealth.org/en/permalink/ahliterature78785
Source
Brain. 2007 Mar;130(Pt 3):862-74
Publication Type
Article
Date
Mar-2007
Author
Carrozzo Rosalba
Dionisi-Vici Carlo
Steuerwald Ulrike
Lucioli Simona
Deodato Federica
Di Giandomenico Sivia
Bertini Enrico
Franke Barbara
Kluijtmans Leo A J
Meschini Maria Chiara
Rizzo Cristiano
Piemonte Fiorella
Rodenburg Richard
Santer René
Santorelli Filippo M
van Rooij Arno
Vermunt-de Koning Diana
Morava Eva
Wevers Ron A
Author Affiliation
Unit of Molecular Medicine, Bambino Gesù Children's Hospital, Rome, Italy.
Source
Brain. 2007 Mar;130(Pt 3):862-74
Date
Mar-2007
Language
English
Publication Type
Article
Keywords
Atlantic Islands - epidemiology
Brain - pathology
Carnitine - blood - urine
DNA Mutational Analysis - methods
DNA, Mitochondrial - genetics
Deafness - epidemiology - genetics - metabolism
Family Health
Female
Gene Frequency - genetics
Humans
Infant
Leigh Disease - epidemiology - genetics - metabolism
Magnetic Resonance Imaging - methods
Male
Methylmalonic Acid - blood - urine
Mitochondrial Encephalomyopathies - epidemiology - genetics - metabolism
Muscle Hypotonia - epidemiology - genetics - metabolism
Muscle, Skeletal - enzymology
Mutation - genetics
Pedigree
Succinate-CoA Ligases - genetics
Abstract
One pedigree with four patients has been recently described with mitochondrial DNA depletion and mutation in SUCLA2 gene leading to succinyl-CoA synthase deficiency. Patients had a Leigh-like encephalomyopathy and deafness but besides the presence of lactic acidosis, the profile of urine organic acid was not reported. We have studied 14 patients with mild 'unlabelled' methylmalonic aciduria (MMA) from 11 families. Eight of the families are from the Faroe Islands, having a common ancestor, and three are from southern Italy. Since the reaction catalysed by succinyl-CoA synthase in the tricarboxylic acid (TCA) cycle represents a distal step of the methylmalonic acid pathway, we investigated the SUCLA2 gene as a candidate gene in our patients. Genetic analysis of the gene in the 14 patients confirmed the defect in all patients and led to the identification of three novel mutations (p.Gly118Arg; p.Arg284Cys; c.534 + 1G --> A). The defect could be convincingly shown at the protein level and our data also confirm the previously described mitochondrial DNA depletion. Defects in SUCLA2 can be found at the metabolite level and are defined by mildly elevated methylmalonic acid and C4-dicarboxylic carnitine concentrations in body fluids in association with variable lactic acidosis. Clinically the diagnosis should be considered in patients with early/neonatal onset encephalomyopathy, dystonia, deafness and Leigh-like MRI abnormalities mainly affecting the putamen and the caudate nuclei. The frequency of the mutated allele in the Faroese population amounted to 2%, corresponding with an estimated homozygote frequency of 1 : 2500. Our data extend knowledge on the genetic defects causing MMA. Our patients present with an early infantile Leigh-like encephalomyopathy with deafness, and later on a progressive dystonia. Mild MMA, lactic acidosis and specific abnormalities in the carnitine ester profile are the biochemical hallmarks of the disease. In view of the frequency of the mutated allele on the Faroe Islands, measures become feasible to prevent the occurrence of the disease on the islands. We confirm and extend the findings on this inborn error of metabolism in the TCA cycle that must be carefully investigated by accurate metabolite analyses.
PubMed ID
17301081 View in PubMed
Less detail

[Syndrome Leigh caused by mutations in the SURF1 gene: clinical and molecular-genetic characteristics]

https://arctichealth.org/en/permalink/ahliterature97127
Source
Zh Nevrol Psikhiatr Im S S Korsakova. 2010;110(1):25-32
Publication Type
Article
Date
2010
Author
P G Tsygankova
S V Mikhailova
E Iu Zakharova
N A Pichkur
E S Il'ina
E A Nikolaeva
G E Rudenskaia
E L Dadali
L M Kolpakchi
I D Fedoniuk
G N Matiushchenko
Source
Zh Nevrol Psikhiatr Im S S Korsakova. 2010;110(1):25-32
Date
2010
Language
Russian
Publication Type
Article
Keywords
Child
Child, Preschool
DNA - genetics
Diagnosis, Differential
Female
Genetic Predisposition to Disease
Genotype
Humans
Infant
Leigh Disease - diagnosis - epidemiology - genetics
Magnetic Resonance Imaging
Male
Membrane Proteins - genetics - metabolism
Mitochondrial Proteins - genetics - metabolism
Mutation
Polymerase Chain Reaction
Prevalence
Russia - epidemiology
Ukraine - epidemiology
Abstract
Syndrome Leigh (SL) or subacute necrotizing encephalomyelopathy - is a rare hereditary genetically heterogeneous disease from the group of mitochondrial encephalomyopathies. Twenty-seven children with SL were examined using clinical, laboratory (measuring lactate levels), MRI and molecular-genetic (polymerase chain reaction genotyping of 9 exons of the SURF1 gene) studies. The mean age of manifestation was 11,6 months. The main manifestations of SL were: delay of psychomotor development, diffuse muscle hypertonic, cerebellar syndrome, ophthalmoparesis, hypertrichosis. The disease had a progressive course with the loss of acquired skills. The blood lactate concentration was increased on average up to 3,1 mM/ml (from 1,9 to 5,1 mM/ml) compared to normal values (1,8 mM/ml). Brain MRI revealed the subcortical and cortical atrophy (80% of cases), symmetrical distinctly delineated hyperintense lesions on T2-weighted images (demyelization) in the basal ganglia and the brain stem (50%), as well as in the cerebellum (25%). Genotyping identified 7 different mutations. The most frequent (64,8%) was the deletion of 2 nucleotides (845delCT) in exon 8 that was in line with early data of Polish researchers thus indicating the Slavic origin of this mutation. Other mutations (574-575insCTGT, 311-321del10insAT and IVS8-1G>) were also frequent in the Russian population.
PubMed ID
20436434 View in PubMed
Less detail

10 records – page 1 of 1.