"A - muscular presentation (maximum 2 points in total): ophthalmoplegia, myopathic facies, exercise intolerance, muscle weakness, rhabdomyolysis, abnormal electromyography (EMG)"
"B - CNS presentation (maximum 2 points in total): developmental delay, loss of skills, stroke-like episode, migraine, seizures, myoclonus, cortical blindness, pyramidal signs (e.g. spasticity), extrapyramidal signs (e.g. dystonia), brainstem involvement"
"Leber hereditary optic neuropathy (LHON)"
"Leber hereditary optic neuropathy (LHON)"
"morphology on histology (maximum 4 points in total): ragged red/blue fibres (4 points), COX-negative fibres (4 points), reduced COX staining (4 points), reduced SDH staining (1 point), SDH positive blood vessels (2 points), abnormal mitochondria on electron microscopy (2 points)"
"morphology on histology (maximum 4 points in total): ragged red/blue fibres (4 points), COX-negative fibres (4 points), reduced COX staining (4 points), reduced SDH staining (1 point), SDH positive blood vessels (2 points), abnormal mitochondria on electron microscopy (2 points)"
"neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP)"
"sensory ataxia neuropathy, dysarthria, and ophthalmoplegia (SANDO)"
"POLG-related disorders"
"POLG-related disorders"
Expected headings
"CNS manifestations"
"B - CNS presentation (maximum 2 points in total): developmental delay, loss of skills, stroke-like episode, migraine, seizures, myoclonus, cortical blindness, pyramidal signs (e.g. spasticity), extrapyramidal signs (e.g. dystonia), brainstem involvement"
"C - multisystem disease (maximum 3 points in total): haematology, gastrointestinal tract, endocrine/growth, heart (e.g. cardiomyopathy), kidney (e.g. renal tubular acidosis), vision, hearing, neuropathy, recurrent/familial"
"additional criteria have been suggested 9: Kreb cycle intermediates (alpha-ketoglutarate, succinate, fumarate) (1 point), ethylmalonic acid and methylmalonic acid (1 point), 3-methylglutaconic acid (1 point)"
"cerebrospinal fluid (CSF) tests: elevated CSF lactate (2 points), elevated CSF protein (1 point), elevated CSF alanine (2 points)"
"additional criteria have been suggested 9: leukoencephalopathy with brainstem and spinal cord involvement pattern on MRI (1 point), cavitating leukoencephalopathy pattern on MRI (1 point), leukoencephalopathy with thalamus involvement on MRI (1 point), deep cerebral white matter involvement with corpus callosum agenesis pattern on MRI (1 point)"
"morphology on histology (maximum 4 points in total): ragged red/blue fibres (4 points), COX-negative fibres (4 points), reduced COX staining (4 points), reduced SDH staining (1 point), SDH positive blood vessels (2 points), abnormal mitochondria on electron microscopy (2 points)"
"There are many conditions that result from mitochondrial dysfunction that affect the neurological, muscular and other bodily systems in a variety of ways, some of these are listed below. Notably, some phenotypes can be caused by either mtDNA or nDNA pathogenic variations (e.g. Leigh syndrome)."
"There are many conditions that result from mitochondrial dysfunction that affect the neurological, muscular and other bodily systems in a variety of ways, some of these are listed below. Notably, some phenotypes can be caused by either mtDNA or nDNA pathogenic variations (e.g. Leigh syndrome)."
"There are many conditions that result from mitochondrial dysfunction that affect the neurological, muscular and other bodily systems in a variety of ways, some of these are listed below. Notably, some phenotypes can be caused by either mtDNA or nDNA pathogenic variations (e.g. Leigh syndrome)."