PROBLEM TO BE SOLVED: To provide a technique for judging the formation and maintenance of a normal higher-order structure of a pathogenic enzyme protein of hereditary metabolic disease when the structural abnormality of the enzyme protein is corrected by a chemical chaperone compound, etc., and to provide a technique for detecting the structural abnormality of an intracellular enzyme protein when the current enzyme replacement therapy and chemistry chaperone therapy are used in combination.SOLUTION: According to the present invention, there is provided a technological basis for detecting the formation and maintenance of the higher order structure of protein when correcting the structural abnormality of a mutant enzyme protein constituting the basis of the present invention. Here, the technological basis is a technique indispensable for analyzing the higher order structure of a pathogenic enzyme protein when the structural abnormality of the enzyme protein, which causes each hereditary metabolic disease, is corrected using a low molecular weight compound (including a chemical chaperone compound) having an affinity for a specific domain of the protein. By using the technological basis, it is possible to search for more effective protein stabilizers or normal folding accelerators. In addition, according to the present invention, it is possible to distinguish between normal and abnormal higher-order structures of intracellular proteins using protease (chymotrypsin). It can be therefore applied to diagnosis, disease type, and prognosis of "Protein mis-folding diseases" including hereditary metabolic diseases. From the above, with the present invention as a technological basis, exploratory researches on more effective intracellular protein stabilizing agents and normal folding accelerators can be accelerated. As a more effective treatment, therefore, it can promote the clinical application of a combination therapy of a chemical chaperone therapy that treats hereditary met
