Inherited metabolic diseases (IMD) or inborn error metabolism (IEM) is a group of diseases in which the genes coding for certain enzymes, transport proteins, membrane receptors, etc. involved in the metabolic process of the body are mutated, leading to disorders in the biochemical metabolism of the body and resulting in the accumulation of intermediary or bypass metabolic products or the lack of final metabolic products, causing a series of clinical symptoms. IEM is mostly autosomal recessive, a few are autosomal dominant or X-linked companion and mitochondrial, etc. Since Garrod put forward the concept of IEM in 1908, more than 500 kinds of diseases have been found so far. Regrettably, however, IEM has long been a forgotten corner of adult neurology, and only in recent years has it begun to receive some attention under the leadership of pediatric neurology colleagues. I have seen a number of well-known hospitals across the country diagnosed as hereditary spastic paraplegia young man, actually methylmalonic aciduria, only with simple vitamin B12 cured; had been diagnosed as primary carnitine deficiency of lipid deposition myopathy of secondary school students, because of the poor conditions of the family can not afford to use the carnitine and give up the treatment, and then due to severe acidosis and life-threatening only when it was found that the glutaric aciduria, only with the simplest vitamin B2 patients get a new life; cerebrovascular disease as the main symptom of the brother and sister in the clinic is actually glycogen accumulation disease type II; diagnosed as torsion spasm, cataracts, psoriasis of the dying elementary school students, but it is actually a biotinidase deficiency, only with biotinidase replacement therapy after the restoration of the beginning; and to the limb pain and sweating as the main symptom of the Fabry disease of the father and daughter who went around to the doctor for many years with no success, there are too many examples. In fact, some of the IEMs in our neurology department are familiar, such as mitochondrial encephalomyopathy, hepatomegaly, dopa-responsive dystonia and adrenoleukodystrophy, etc. However, there are more than 500 genetic metabolic diseases, and the ones that we have recognized are only a handful of them. It can be said that there are at least as many inherited metabolic diseases as there are enzymes in the body. Let’s say, under normal circumstances, A is used as a substrate to produce B under the action of enzyme E and coenzyme F. Once the activity of E or F is partially or completely lost, a large amount of A accumulates in the body and produces the harmful substance b through the bypass pathway, which, together with the lack of B, results in the damage of the nervous system, the liver and kidneys, the skin, and the hematopoietic system, among others. On the other hand, because the degree of enzyme deficiency varies, the patient’s symptoms may be mild or severe, and thus all inherited metabolic disorders have neonatal, juvenile, and adult late-onset forms. Some people die prematurely right after birth, while others do not develop the disease throughout their lives, or it is only in adulthood that it becomes prominent due to a sudden change in diet or a major stressful event such as trauma or infection. Late-onset IEM is often characterized by neuromuscular symptoms, so it is often the first to be seen in our adult neurology department, which poses a great challenge to us. We have to look for traces of IEM through detailed medical history, maternal history, family history, dietary habits and morbidity patterns, combined with blood and urine routine, biochemical analysis, blood ammonia, blood lactate, blood homocysteine and other simple tests, which often lead to unexpected gains and bring new life to the patients. IEM can be directly classified according to the metabolic substrates involved into abnormalities of glucose metabolism (e.g., acid maltase deficiency, fructose-1,6-bisphosphatase deficiency), abnormalities of amino acid metabolism (phenylketonuria, urea cycle disorders), organic acid disorders (glutaric aciduria, methylmalonic aciduria), abnormalities of fatty acid metabolism (multiple acyl CoA dehydrogenation deficiency), abnormalities of nucleic acid metabolism (adenosine deaminase deficiency), and abnormalities of metal metabolism (adenosine deaminase deficiency). deficiency), and abnormal metal metabolism (Wilson’s disease), among others. According to the molecular size of abnormal metabolites, IEM can be divided into small molecule disease (such as organic acid metabolism) and organelle disease (such as lysosomal storage disease and mitochondrial encephalomyopathy). The former has a rapid onset of disease, a recurrent course, a lack of physical examination and pathological features, and a significant therapeutic effect; the latter has a gradual onset of disease, progressive exacerbation, and often has relatively specific physical examination or pathologic changes, and responds poorly to the general treatment. Poor response, the most common is mitochondrial encephalomyopathy, muscle biopsy histopathology can have typical broken red fibers (RRF), at present by our neuromuscular pathology laboratory diagnosis of mitochondrial encephalomyopathy cases have nearly 200 cases. Laboratory diagnosis of IEM should be made according to the characteristics of history and symptoms from simple to complex, from initial screening to precise, and according to certain step selection. It mainly includes blood and urine routine, blood biochemical analysis, qualitative or quantitative analysis of amino acids, analysis of organic acids and lipoyl carnitine, analysis of long-chain and very long-chain fatty acids, analysis of purines and pyrimidines, analysis of carbohydrates and sugar alcohols, analysis of oligosaccharides and mucopolysaccharides, enzyme analysis and DNA analysis. The application of biochemical methods to determine abnormal metabolites in a variety of diagnostic methods is currently the main method of diagnosis of inherited metabolic diseases, urine, blood, cerebrospinal fluid, tissue biopsy and other routine laboratory findings can suggest the possibility of inherited metabolic diseases, which helps to select further examination projects. As medical workers, especially pediatricians, have improved their understanding of inherited metabolic diseases, a considerable number of hospitals in major cities in China have routinely carried out tests such as lactic acid, pyruvic acid, blood ammonia, blood gas analysis, and urine screening, which enable initial screening for certain amino acid and organic acid or energy metabolism deficiency diseases. Amino acid analysis is an important means of diagnosing genetic metabolic diseases, and most of them are now quantitatively analyzed by automatic amino acid analyzers, high-performance liquid chromatographs or tandem mass spectrometers, which is helpful for diagnosing complex amino acid diseases. Indications for blood and urine amino acid analysis include: ① family has been diagnosed with a certain genetic metabolic disease patients or similar symptoms; ② highly suspected amino acid, organic acid and energy metabolism defects; ③ unexplained metabolic anomalies (metabolic acidosis, anion gap increase, hyperammonemia, hypoglycemia, ketonuria, aciduria, blood uric acid content decreased, etc.); ④ renal disorders (stones, tubular dysfunction, Fanconi, etc.), Renal disorders (stones, abnormal tubular function, Fanconi syndrome); ⑤ crystal dislocation or cataract; ⑥ epileptic encephalopathy; ⑦ abnormal hair color or peculiar body odor; ⑧ effective dietary treatment. We have used amino acid analysis to diagnose a case of branched-chain α-ketoacid dehydrogenase deficiency (maple glucosuria), which belonged to the vitamin B1-sensitive type of maple glucosuria, and the disease did not progress after vitamin B1 supplementation. The application of gas chromatography or gas chromatography-mass spectrometry for the quantitative and qualitative analysis of various organic acids in body fluids (urine, plasma, and cerebrospinal fluid) can provide extremely valuable information on the status of various metabolic pathways in the body, and it is an important tool for high-risk screening and diagnosis of inherited metabolic diseases. The indications for organic acid analysis are: ① unexplained metabolic abnormalities (metabolic acidosis, increased blood lactate, increased anion gap, non-ketotic hypoglycemia, hyperammonemia, etc.); ② toxic symptoms; ③ suspected organic acid or amino acid disease; ④ suspected fatty acid oxidation disorders and energy metabolism disorders; ⑤ unexplained hepatomegaly; ⑥ unexplained neuromuscular disease; ⑦ unexplained leukoencephalopathy; (8) Progressive damage of multiple systems, etc. The application of tandem mass spectrometry to determine the amino acid and acylcarnitine profiles in filter paper blood samples can rapidly screen for more than 30 genetic metabolic diseases including amino acid diseases, organic acidemia and fatty acid oxidation defects within minutes, realizing the detection of multiple diseases in a single experiment. However, some screen-positive cases need to be analyzed by qualitative/quantitative analysis of organic or amino acids again to confirm the diagnosis. The diagnosis of certain inherited metabolic diseases requires biopsies, including skin, conjunctiva, liver and muscle biopsies. Sometimes the diagnosis can be made from the histologic appearance or ultrastructure of the specimen, and sometimes further DNA and enzyme tests are required. For some cases with high suspicion of IEM or unexplained death, body fluids or tissue specimens should be obtained at autopsy, which often provides an important basis for the final diagnosis. The therapeutic goal of inherited metabolic diseases is to correct the metabolic defects and the pathophysiologic changes they cause, and the main principles of therapeutic management include controlling the intake of defective enzyme substrates, enzyme substitution therapy, promoting the excretion of toxic metabolites, replacement of end metabolites, enzyme cofactor substitution therapy, gene therapy, and symptomatic supportive management. As a new generation of clinicians, it is our duty and obligation to emphasize the diagnosis and treatment of IEM.