Table 3
Summary of diagnostic features in selected metabolic diseases in which vacuolated lymphocytes may be identified in peripheral blood films
| Disease | OMIM | Enzyme defect | Genetics | Lymphocyte characteristics | Gold standard for diagnosis |
|---|---|---|---|---|---|
| AR, autosomal recessive; MPS, mucopolysaccharidosis; PAS, periodic acid Schiff. | |||||
| Pompe’s disease (glycogen storage disease type 2) Adult acid maltase deficiency | 232300 | Acid α1,4-glucosidase (acid maltase) deficiency | AR; 17q25.2–q25.3; mutations in the gene encoding acid α glucosidase (GAA) | 1–6 small, discrete, PAS positive vacuoles | Enzyme assay on cultured fibroblasts |
| Salla disease (sialic acid storage disease) | 269920 604369 | Sialin (sialic acid transporter protein) deficiency | AR; 6q14–q15; mutations in SLC17A5 | Numerous small vacuoles | Urine analysis for sialic acid; vacuolated lymphocytes |
| Sialidosis type 2 | 256550 | Neuraminidase deficiency | AR; 6p21.3 | Numerous large bold vacuoles | Enzyme assay of cultured fibroblasts |
| Neuraminidase deficiency with α galactosidase deficiency (galactosialidosis) | 256540 | α Neuraminidase and α galactosidase deficiency secondary to cathepsin A/lysosomal protective protein deficiency | AR; 20q13.1 | Numerous large bold vacuoles | Enzyme assay of cultured fibroblasts; histochemical β galactosidase detection on blood films, but neuraminidase not possible on blood films |
| I cell disease (muco-lipidosis II) | 252500 | N-Acetyl glucosaminyl-phosphotransferase deficiency | AR; 4q21–23 | Numerous large bold vacuoles | Iso-screen of plasma for aryl sulfatase A; fibroblast culture in which all lysosomal enzymes are negative |
| GM1 ganglosidosis | 230500 | β Galactosidase deficiency | AR; 3p21.33 | Numerous large bold vacuoles; eosinophil granules are large, grey, and sparse | Enzyme assay of white blood cells and fibroblasts; histochemical β-galactosidase detection on blood films, absent in lymphocytes and neutrophils |
| MPS 1H (Hurler) | 607014 | αL-Idurinidase deficiency | AR; 4p16.3 | Occasional vacuoles in occasional lymphocytes, some with basophilic inclusions (Gasser cells); metachromatic inclusions in <5% of lymphocytes; vacuoles in 5–10% of lymphocytes in MPS 1H/S | Enzyme assay on white blood cells; urinary glycosaminoglycans |
| MPS 1S (Scheie) | |||||
| MPS 1H/S (Hurler-Scheie) | 607016 | ||||
| MPS 2 (Hunter) | 309900 | Iduronate sulfatase deficiency | X linked; Xq28 | Occasional lymphocyte with occasional vacuoles; metachromatic inclusions in <20% of lymphocytes | Enzyme assay on white blood cells; urinary glycosaminoglycans |
| MPS 3 (San filippo) | |||||
| A | 252900 | Heparan sulfate sulfatase | AR; 17q25.3 | Occasional lymphocytes with occasional vacuoles; metachromatic inclusions in >20% of lymphocytes | Enzyme assay on white blood cells; urinary glycosaminoglycans |
| B | 252920 | N-Acetyl-α-D-glucosamidase | AR; 17q21 | ||
| C | 252930 | Acetyl-CoA-α-glucosamide-N-acetyl transferase | AR; Chr 14 | ||
| D | 252940 | N-Acetyl glucosamine 6-sulfatase | AR; 12q14 | ||
| MPS 4 (Morquio) | |||||
| A | 253000 | Galactosamine 6 sulfatase deficiency | AR; 16q24.3 | No vacuoles; no metachromasia; occasional basophilic inclusions; small vacuoles in many lymphocytes; no metachromasia | Enzyme assay on white blood cells; undetectable β galactosidase activity in blood films; urinary glycosaminoglycans |
| B | 253010 | β Galactosidase deficiency | AR; ??3p21.33 | ||
| MPS 6 (Maroteaux-Lamy) | 253200 | Aryl sulfatase B deficiency | AR; 5q11–q13 | Small vacuoles present in a considerable number of lymphocytes; metachromatic inclusions in lymphocytes; Alder granulation (basophilic, birefringent, metachromatic granules) in all neutrophils | Enzyme assay of white blood cells; urinary glycosaminoglycans |
| MPS 7 | 253220 | β Glucuronidase deficiency | AR; 7q21.11 | Occasional lymphocytes with small vacuoles | Enzyme assay of white blood cells; urinary glycosaminoglycans; β glucoronidase activity absent in lymphocytes and neutrophils in blood films |
| Niemann-Pick A | 257200 | Sphingomyelinase deficiency | 11p15.4–p15.1 | 1–6 small vacuoles in most lymphocytes | Enzyme assay of white blood cells |
| Fucosidosis | 230000 | Α-L-Fucosidase | AR 1p34 | Small discrete vacuoles in lymphocytes | Enzyme assay of white blood cells |
| Juvenile Batten’s disease (NCL3) | 204200 | Not known | AR 16p12.1 | Numerous, large, bold vacuoles in considerable number of lymphocytes | Molecular analysis shows a 1 kb deletion in NCL3; skin biopsy shows fingerprint inclusions in sweat glands on electron microscopy; fingerprint profiles can also be seen in some lymphocytes on electron microscopy |
| Mannosidosis | 248500 | α Mannosidase | AR; 19cen–q12 | Variable from numerous small discrete to several large bold vacuoles in lymphocytes | Enzyme assay of white blood cells |
| Wolman’s disease | 278000 | Acid esterase (acid lipase, acid cholesterol ester hydrolase) | AR; 10q24–q25 | 1–6 small discrete vacuoles in most lymphocytes, which stain positive with oil red o or Sudan black lipid stains | Enzyme assay of white blood cells; absence of acid esterase can be detected in blood films |
