Leigh syndrome, also known as subacute necrotizing encephalomyelopathy, is a hereditary progressive neurological degenerative disease. 1951 British neuropathologist Denis Leigh first described a case of a 7-month-old infant who presented with loss of pupillary light reflexes, limb tonicity, and deafness. In 1996, Rahman et al. proposed diagnostic criteria for LS: progressive neurological disease, including motor and mental retardation; signs and symptoms of basal ganglia and/or brainstem involvement; elevated blood and/or cerebrospinal fluid lactate levels; and one or more of the following: leigh In 1989 Miranda et al first proposed LS as an inherited disease. in 1992 Tatuchet al identified the mtDNA 8993T>G point mutation as the causative mutation in maternally inherited LS. Since then, mitochondrial and nuclear mutations that cause LS have been reported. The clinical manifestations of LS are diverse and can involve the central and/or peripheral nervous system, muscles, and other systems such as the endocrine, gastrointestinal, and cardiac systems. Most children die before the age of 2 years and adult onset is very rare and easily misdiagnosed. Typical LS usually starts in infants or children and presents with progressive mental-intellectual and motor regression, limb weakness, ataxia, convulsions, feeding difficulties, vomiting, vision and hearing loss, oculomotor disorders and other cranial nerve damage. Children often have paroxysmal central respiratory dysfunction or even respiratory failure, and some patients also have peripheral nerve and spinal cord damage. The onset of the disease is rapid and death occurs within 2 years of age. The onset of the disease in adults is very rare. It can be insidious or acute due to fever, fatigue, hunger and other stimuli, and gradually develops spastic paraplegia, ataxia, motor intolerance, myocardial damage, nystagmus, strabismus, vision loss and Parkinson’s-like symptoms, making early diagnosis more difficult. The typical LS imaging manifestations are mainly abnormal long T1 and long T2 signals in the nucleus accumbens, caudate nucleus, thalamus, brainstem (including the gray matter around the aqueduct, dorsal cap, substantia nigra, and red nucleus), and cerebellar dentate nucleus. The posterior part of the nucleus accumbens, the dorsal medial thalamic nucleus and the periaqueductal gray matter of the brainstem are relatively typical sites of involvement. In a small number of patients, only cerebral atrophy and/or cerebral white matter lesions may be seen, resembling cerebral leukodystrophy-like changes, especially the posterior part of the hemianopia and the corpus callosum are commonly involved, progressing from posterior to anterior, similar to adrenal cerebral leukodystrophy. Typical LS pathology is mostly symmetrical necrotic lesions, commonly in the nucleus accumbens, caudate nucleus, thalamus, brainstem, cerebellopontine nucleus, posterior cord of the spinal cord and pyramidal tract. The optic nerve, nerve roots, peripheral nerves, and white matter of the brain may also be involved. Microscopically, vascular hyperplasia without hemorrhage, swelling of neuronal cell bodies and nuclei, chromatin lysis, and gliosis are seen. The midbrain nucleus accumbens is clearly involved, while the papillae are preserved. The medulla oblongata lesions are often confined to the inferior olivary nucleus, the spinal cord lesions are often located in the posterior cord, commonly in the cervical spinal cord, and the inferior spinal cord is usually not involved. The diagnosis of LS requires a combination of clinical manifestations, blood and cerebrospinal fluid examinations, especially biochemical and metabolic screening, imaging manifestations, and neuropathological changes. 1996 Rahman et al. proposed diagnostic criteria for LS based on these four aspects, especially the typical imaging manifestations combined with clinical manifestations provide important clues for early clinical diagnosis. However, in recent years, reports on the pathogenesis and genetic basis of LS have increased year by year, and enzymatic assays of relevant metabolic links and corresponding genetic tests have facilitated the early clinical confirmation of the diagnosis. The differential diagnosis mainly requires the exclusion of ischemic-hypoxic encephalopathy, carbon monoxide and other toxic poisoning, hepatomegaly, Wernicke’s encephalopathy, and extra-pontine myelinolysis. For patients suspected of LS, in addition to routine biochemical tests, attention should be paid to blood lactate, blood gas analysis, muscle enzyme profile, etc. For patients whose clinical diagnosis is likely to be LS, further mitochondrial electron respiratory chain complex enzyme activity and LS-related genetic tests can be measured. Patients with confirmed diagnosis should be given early nutritional support and cocktail therapy including multivitamins, L-carnitine, coenzyme Q10, creatine monohydrate, etc. Especially when the patient is hyperthermic, the conflict between energy supply and demand increases, and caloric supplementation should be actively pursued.