The role of ultrastructural examination in storage diseases

Storage diseases (SDs) are rare metabolic disorders characterized by the intra- or extralysosomal accumulation of unmetabolized compounds. Different causes determine the buildup of undigested material, resulting in typical histochemical and ultrastructural changes. Ultrastructural examination of tissue from patients with clinically suspected SDs may disclose pathognomonic alterations or suggest a differential diagnosis even in the absence of clinically evident involvement of the biopsied tissue. Accurate diagnosis of SDs requires a continuous integration of clinical, biochemical, ultrastructural, and, when available, molecular data. It is also important for the pathologist to be familiar with the morphological variability characterizing each SD, because some morphologies are often the early stages of undeveloped forms and morphologically similar diseases are easily confused. The major advantages of transmission electron microscopy (TEM) techniques are discussed, emphasizing the current role of TEM as a rapid, cost-effective, and efficient diagnostic tool.