The pathologist's approach to the diagnosis of metabolic disease

Many inborn errors of metabolism have tissue changes that suggest or indicate a diagnosis on morphologic bases. This emphasizes the involvement of the pathologist in the study of tissues obtained by biopsy as part of the diagnostic workup of cases with clinical evidence suggesting a metabolic disorder. Some of these diseases involve proteins with enzymatic activity with a consequent backlog of precursor metabolites. If these metabolites are insoluble or compartmentalized in cells, they accumulate in tissues. The diagnosis in those cases rests on establishing the nature of the accumulated materials and their topographic distribution. In some storage diseases, the abnormal substance can be identified in the affected tissues by histochemistry or ultrastructure. Another group of inborn disorders of metabolism produce changes in subcellular organelles such as peroxisomes and mitochondria. A third group is expressed by rather unique tissue changes which strongly suggest the diagnosis of metabolic disease.