Urine, in the eyes of most people, is considered a metabolic waste of the body, but for the laboratory physicians of the Key Laboratory of Genetic Metabolic Diseases at the Provincial Children's Hospital, one drop of urine can currently diagnose more than 40 organic acid metabolic diseases. Xiaoming (pseudonym), who is over 3 years old, is a beneficiary of this urine organic acid detection technology. Xiaoming has been walking unsteadily since birth. A few days ago, the child complained of pain in the left lower limb and came for further diagnosis and treatment. The family took Xiaoming to the Provincial Children's Hospital for examination using urine organic acid testing technology, and confirmed that the cause of the child's movement disorder was an organic acid urinary disorder called methylmalonic acid. If left untreated, the child may become disabled or even die. Through timely medication treatment, rehabilitation training, and regular monitoring, Xiaoming's condition is now under control and his level of physical development has significantly improved.
1、 What is organic acidosis?
Due to mutations in certain specific enzyme genes, the accumulation of related carboxylic acids and their metabolites in the body increases, blood concentrations rise, and they are excreted in large quantities from urine, leading to organic acidosis. Organic acidosis is mostly an autosomal recessive genetic disease. The incidence rate of a single disease is relatively low, but the overall incidence rate is not low due to the variety of diseases. Since Tanaka diagnosed the first case of isovalerianemia by gas chromatography mass spectrometry (GC-MS) in 1966, more than 40 diseases have been found so far, of which methylmalonic aciduria is the most common organic aciduria in children.
2、 The sources of organic acids
Understanding what organic aciduria is, where are the sources of organic acids? Organic acids are intermediate products (carboxylic acids) produced during metabolic processes such as amino acid degradation, glycolysis, fatty acid oxidation, steroids, drugs, or special diets in the body, and are excreted through urine. Why should we pay attention to organic acid testing? It is because some organic acids have toxic effects, and abnormal accumulation can cause multi organ damage, especially neurological damage, which can have adverse effects on the body and even cause death.
3、 What are the clinical manifestations of patients with organic acidosis?
The clinical manifestations of patients are complex and vary greatly among individuals. Some patients may experience acute onset in newborns and infants, while others may present with progressive neurological damage such as intellectual disability, seizures, and motor disorders. Some patients may experience intermittent attacks, often triggered by infections, hunger, fatigue, and other factors, resulting in vomiting, metabolic acidosis, hyperammonemia, hypoglycemia, consciousness disorders, and even sudden death.
4、 What is the experimental method for detecting organic acids in urine?
Urine organic acid detection usually uses gas chromatography-mass spectrometry (GC-MS), whose basic principle is to use the separation ability of the gas chromatography column to separate the components in the sample, and further identify the separated components using a mass spectrometer (qualitative analysis), and finally calculate the accurate amount of each component (quantitative analysis). GC-MS has specificity in the diagnosis of organic aciduria and can assist in the diagnosis of amino acid and fatty acid oxidative metabolic diseases in children. It can be used for prenatal diagnosis of organic aciduria. Individuals with significantly abnormal detection parameters can be directly diagnosed with diseases. Some diseases require analysis based on blood tandem mass spectrometry detection results, while others require combined genetic testing for diagnosis.
5、 What diseases can be detected by urine organic acid testing?
Urine organic acid GC/MS detection can detect more than 40 types of organic acid urinary disorders, such as organic acid metabolism disorders (such as methylmalonic acid urinary disorders, propionic acid urinary disorders, and isovaleric acid urinary disorders), some amino acid metabolism disorders (such as hyperphenylalaninemia, urea cycle disorders, etc.), and some fatty acid metabolism abnormalities (short chain acyl CoA dehydrogenase deficiency, multiple acyl CoA dehydrogenase deficiency, etc.), which can be used as an auxiliary diagnosis for genetic metabolic diseases.
6、 How to retain, store, and transport urine organic acid test specimens?
1. Fresh morning urine is best, or random urine. Generally, 5-10 milliliters should be taken and placed in a specialized container for laboratory testing. Within 24 hours of arrival at the laboratory, it should be stored and transported at 4 ℃ for refrigeration. If stored for more than 24 hours, it should be stored and transported at -20 ℃ for freezing.
2. Urine filter paper sheets, ≥ 3 sheets, dried and refrigerated, should be stored at 4 ℃ for testing.