Electron microscopy in the diagnosis of lysosomal storage diseases

Lysosomal storage diseases (LSD) affect cells of the conjunctiva in the absence of clinical eye findings. Consequently conjunctiva was added to skin, rectal mucosa, and peripheral blood lymphocytes as a biopsy site for electron microscopic examination in suspected LSD. The abnormally stored substrates in LSD are the result of diminished lysosomal enzyme activity. Although all cells lack the deficient lysosomal enzyme, the quantity of stored material varies with the extent of breakdown of substrate in the cell under normal circumstances. The stored material does not accumulate in all cells and may have a different cellular morphology at different sites. Although no one tissue provides universally diagnostic material for electron microscopy, skin and conjunctiva are optimal for most LSD. Rectal mucosa and peripheral blood lymphocytes arc also useful in many cases. Biochemical assays have replaced brain biopsy for diagnosis but these techniques may give equivocal or non‐diagnostic results, and in some diseases the enzyme defect remains undefined. Of the 359 biopsies of conjunctiva, skin, rectal mucosa, and lymphocytes we evaluated for LSD and other neurodegenerative diseases, 65 showed abnormal lysosomal storage; in 41 a specific diagnosis was made by biochemical assay or morphology. Ultrastructural examination of tissue from patients with clinically suspected storage disease may disclose pathognomonic alterations or suggest a differential diagnosis even in the absence of clinically evident involvement of the biopsied tissue. Biopsy has particular value in those diseases with incompletely characterized biochemical abnormalities.