"POLG-related disorders, or polymerase gamma-related disorders, describes a spectrum of genetic mitochondrial disorders with overlapping phenotypes, due to nuclear mutations in POLG1 or POLG2."
"The four main POLG-related disorders are:"
"POLG-related disorders are very rare, with the most common subtype having an incidence of approximately one in 50,000 people 1."
"Also known as Alpers-Huttenlocher syndrome, and previously as progressive cerebral poliodystrophy, this is the most well-studied POLG-related disorder 2-6. It describes a childhood-onset progressive and severe encephalopathy with patients presenting with the classic triad of 2-5:"
"The polymerase gamma (POLG) gene (POLG1) is located on the long arm of chromosome 15 and encodes for DNA polymerase γ, while the POLG2 gene, located on the long arm of chromosome 17, encodes for its catalytic accessory subunit 2,3,7. Damage to either of these genes result in uncontrolled mtDNA defects which result in a very varied clinical phenotype that changes across a patient’s lifespan 2,3,7."
"Generally, mutations to POLG2 only result in autosomal dominant PEO, while mutations to POLG1 result in any other POLG-related disorder, all of which are inherited in an autosomal recessive pattern 2,3,7."
"Radiographic features of POLG-related disorders are not well-described beyond case series-level evidence whereby neuroimaging features of POLG-related disorders featuring epilepsy, such as Alpers syndrome, are most commonly described 8-13."
"Prognosis depends on the specific POLG-related disorder present and the degree of epilepsy control and multiorgan dysfunction, but is generally poor 4,8."
"Also known as Alpers-Huttenlocher syndrome, and previously as progressive cerebral poliodystrophy, this is the most well-studied POLG-related disorder 2-6. It describes a childhood-onset progressive and severe encephalopathy with patients presenting with the classic triad of 2-5:"
"Also known as Alpers-Huttenlocher syndrome, and previously as progressive cerebral poliodystrophy, this is the most well-studied POLG-related disorder 2-6. It describes a childhood-onset progressive and severe encephalopathy with patients presenting with the classic triad of 2-5:"
"A childhood-onset form also exists, known as childhood myocerebrohepatopathy spectrum (MCHS), which shares the same clinical presentation 2,3. In some patients Alpers syndrome may exist without liver failure, and the term Alpers-like encephalopathy is used in these cases 2,3."
"A childhood-onset form also exists, known as childhood myocerebrohepatopathy spectrum (MCHS), which shares the same clinical presentation 2,3. In some patients Alpers syndrome may exist without liver failure, and the term Alpers-like encephalopathy is used in these cases 2,3."
"sensory ataxia neuropathy, dysarthria, and ophthalmoplegia (SANDO)"
Expected headings
"Alpers syndrome"
"Ataxia neuropathy spectrum"
"Progressive external ophthalmoplegia"
"Myoclonic epilepsy myopathy sensory ataxia"
"Generally, a group of syndromes characterised by sensory or cerebellar ataxia and peripheral sensory neuropathy, although approximately two-thirds also develop epilepsy, often myoclonic, and half also develop ophthalmoplegia 2,3,5."
"autosomal dominant (adPEO): PEO with systemic involvement such as generalised myopathy, sensorineural hearing loss, parkinsonism, ataxia, neuropathy, ovarian failure, and psychiatric symptoms 2,3,5"