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Vacuolated lymphocytes–a diagnostic clue

A 2-yr-old boy presented with lethargy, weakness, delayed development, recent regression of developmental milestones and ataxia. A full blood count revealed a hemoglobin 125 g ⁄L, white cell count 8 · 10 ⁄L, neutrophil count 2.2 · 10 ⁄L and a platelet count 346 · 10 ⁄L. Magnetic resonance imaging (MRI) scan of the brain showed bilateral, symmetrical white matter signal change in the periventricular, subcortical and deep white matter. The MRI changes raised the possibility of a metabolic disorder. Examination of the peripheral blood film revealed the presence of vacuolated lymphocytes with the lymphocyte morphology varying from lymphocytes with a few vacuoles to some lymphocytes showing a cytoplasm packed with well-defined vacuoles. No other significant morphological abnormality was noted on the blood film (Fig. 1). Analysis of white cell enzymes revealed markedly reduced levels of the enzymes aryl sulfatase A and aryl sulfatase B, thus confirming the diagnosis of multiple sulfatase deficiency. The child was lost to follow-up. Vacuolated lymphocytes occur most commonly as the peripheral blood manifestation of inherited metabolic disorders (1). Rarely, they may occur as part of a congenital anomaly (Jordan’s anomaly) or in reactive conditions. When present, lymphocyte vacuolation is manifested as clear, sharply defined vacuoles in the lymphocyte cytoplasm. The inherited metabolic disorders associated with vacuolated lymphocytes include Niemann-Pick disease Type A, infantile sialic acid storage disorder, Wolman’s disease, Mucolipidoses II and III, Salla disease, mannosidosis, Batten disease, GM1 gangliosidosis, neuraminidase deficiency, galactosidosis, fucosidosis, Pompe’s disease, aspartylglycosaminuria and rarely, multiple sulfatase deficiency (2). The metabolic product, which causes vacuolation, depends on the specific enzyme deficiency. Multiple sulfatase deficiency results from a deficiency of the aryl sulfatase A, B and C enzymes causing accumulation of sulfatides, mucopolysaccharides, steroid sulfites and gangliosides. Clinical features include coarse facies, developmental delay and regression and in some cases, hepatosplenomegaly and icthyosis. There are only rare case reports of vacuolated lymphocytes in multiple sulfatase deficiency. The technique of blood film examination is crucial in the detection of vacuolated lymphocytes (3, 4). It should be noted that during preparation of the standard blood film the abnormal, vacuolated lymphocytes are preferentially drawn to the tail portion of the film, either because of their size or because of their density or both (4). Hence, the tail end of the film should be carefully examined when looking for vacuolated lymphocytes. Ideally, about six blood films should be made from freshly collected, EDTA anticoagulated blood by an experienced technician. An average of 100 lymphocytes should be examined, and a note should be made of the characteristics and extent of vacuolation (3). In conclusion, thorough examination of a well-prepared peripheral blood film for vacuolated lymphocytes provides an important clue to the presence of inherited metabolic disorders in an appropriate clinical setting.