Five of them harbored mtDNA deletions associated with Kearns-Sayre syndrome (KSS), one had a mitochondrial point mutation at the mtDNA ATPase6 gene, and one had a POLG mutation.
We present a pediatric patient with 13 and 70 trinucleotide CAG repeats within SCA7 gene and no family history, whose presentation mimicked Kearns-Sayre syndrome (KSS).
To gain further insight into the pathogenesis of cerebellar dysfunction in KSS, antibodies against synaptophysin (SY) were used to identify presynaptic terminals and antibodies to calbindin D (CB) to identify Purkinje cells in the cerebellar cortex and in the dentate nucleus from two autopsied cases of KSS.
Cerebellar ataxia is common in myoclonic epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions, in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28 and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to mutations in nuclear genes involved in mitochondrial morphology or function.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
We found a case of KSS, who initially presented endocrinological dysfunction such as insulin-dependent diabetes mellitus (IDDM) and growth hormone (GH) deficiency, and had not developed external ophthalmoplegia until the age of 17.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
Treatment with the specific LOX inhibitor beta-aminopropionitrile decreased the contraction difference between KSS and normal human fibroblast equivalents.
In a Kearns-Sayre syndromeMAG loss region, high levels of mtDNA deletions together with cytochrome- c oxidase-deficient cells and loss of mitochondrial respiratory chain subunits (more prominent in the white than gray matter and glia than axons) confirmed the pathogenicity of mtDNA deletions.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
Besides demonstrating remarkable similarities in the lesion profile of KSS and FL-PGC-1a-deficient mice, this study first provides morphological evidence for the identical origin of WM and GM vacuolation as well as for the presence of intracytoplasmic oligodendroglial vacuoles in mitochondriopathies.
Our genetic and metabolomics analyses suggest that CAFSA is a heterogeneous entity related to mitochondrial DNA alterations either through POLG mutations or a mechanism similar to what is observed in Kearns-Sayre syndrome.
These predominant breakpoint regions are similar to those described in other conditions with multiple deletions, such as autosomal dominant progressive external ophthalmoplegia (adPEO) and normal aging, but different from those described in diseases due to single deletions such as Kearns-Sayre syndrome and sporadic PEO.
Cerebellar ataxia is common in myoclonic epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions, in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28 and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to mutations in nuclear genes involved in mitochondrial morphology or function.
Histopathological comparison of Kearns-Sayre syndrome and PGC-1α-deficient mice suggests a novel concept for vacuole formation in mitochondrial encephalopathy.
Finally, the transcription of the nuclear ATPsyn.beta and ANT1 genes was induced in parallel with the high level of mtDNA transcripts in MERRF and MELAS muscle, but was repressed in KSS muscle.
To report the RRM2B mutation frequency in adults with multiple mtDNA deletions and examine RNR assembly in a patient with Kearns-Sayre syndrome (KSS) caused by two novel RRM2B mutations.
To report the RRM2B mutation frequency in adults with multiple mtDNA deletions and examine RNR assembly in a patient with Kearns-Sayre syndrome (KSS) caused by two novel RRM2B mutations.
At follow-up, HSS was to 89.7 in the FuZion® group and 89.0 in the standard group, KSS (clinical) was 92.6 in and 91.3 respectively, and KSS (Functional) was 91.0 in the FuZion® group and 87.6 in the standard group.
Finally, the transcription of the nuclear ATPsyn.beta and ANT1 genes was induced in parallel with the high level of mtDNA transcripts in MERRF and MELAS muscle, but was repressed in KSS muscle.