[TS4-1D-1] Role of gene analysis in early diagnosis of inherited metabolic diseases
Many inborn errors of metabolism can be diagnosed by genetic testing such as biochemical examination and enzyme activity measurement. For example, diagnosis of homocystinuria is carried out by high methionine in neonatal mass screening, high total blood homocysteine in examinations, and increased urinary homocystine excretion by urinary amino acid analysis. However, when clear high blood homocysteine levels are not recognized, it is necessary to perform enzyme diagnosis and gene analysis. Diagnosis of urea cycle disorders is confirmed by the presence of hyperammonemia and further analysis of blood and urinary amino acids lead to diagnosis of OTC deficiency, citrullinemia, argininosuccinuricuria, argininemia However, NAGS deficiency and CPS1 deficiency cannot be distinguished by biochemical examination. Diagnosis is possible by confirming the mutation of NAGS or CPS1 gene by gene analysis. In addition, distinction between OTC deficiency and NAGS deficiency or CPS1 deficiency might be difficult. Therefore, gene analysis of OTC deficiency is sometimes performed.
Genetic analysis is also useful for inherited metabolic diseases requiring prenatal diagnosis. In GSD type 1a and citrin deficiency, biochemical diagnosis is difficult and high-frequency mutations in Japanese are known, so if we suspect these diseases, we will conduct gene analysis during early stage and confirm the diagnosis. Thus, in diagnosis of inherited metabolic diseases, early diagnosis is possible by conducting genetic testing, but the role of gene analysis is also considered to be important.
Genetic analysis is also useful for inherited metabolic diseases requiring prenatal diagnosis. In GSD type 1a and citrin deficiency, biochemical diagnosis is difficult and high-frequency mutations in Japanese are known, so if we suspect these diseases, we will conduct gene analysis during early stage and confirm the diagnosis. Thus, in diagnosis of inherited metabolic diseases, early diagnosis is possible by conducting genetic testing, but the role of gene analysis is also considered to be important.