Cytoplasmic Vacuoles in Lymphocytes of a Child with Sialic Acid Storage Disorder

Abstract

This is an image-based clinical vignette demonstrating unusual cytoplasmic vacuoles in the lymphocytes in a stained peripheral blood smear from a 6-month-old infant who presented with seizures, hypotonia, and hepatosplenomegaly and was found to have the extremely rare lysosomal disorder, namely, sialic acid storage disease. Although not specific, it is important to recognize this morphologic finding for reflex biochemical and genetic testing.

Keywords

hypomyelination - infantile sialic acid storage disorder - lysosomal membrane transporter - N-acetylneuraminic acid - sialic acid

Image and Case Description

This is a composite of photomicrographs showing lymphocytes with cytoplasmic vacuoles noted upon review of a stained peripheral blood smear from a 6-month-old infant who presented with a complaint of seizures and was found to have hypotonia and hepatosplenomegaly ([Fig. 1]). At the time of review, the complete blood count (CBC) data included the following: white blood cell (WBC) = 6.5 × 10⁹/L; hemoglobin = 14.2 mg/L; and platelets = 86 × 10⁹/L. A storage disease was suspected and workup to establish the diagnosis included total sialic acid (18,966 nmol/mg) and free sialic acid (18,575 nmol/mg), both of which were significantly elevated.

Fig. 1 Peripheral smear showing lymphocytes with multiple vacuoles in the cytoplasm. Figure magnification: ×100 oil.

Comments

Sialic acid storage disease is a rare lysosomal disorder, inherited as an autosomal recessive condition, rendering cells unable to clear sialic acid.[1] An underlying genetic defect in 1 of more than 40 possible genes that control this process can result in intracellular accumulation/storage of the sugar N-acetylneuraminic acid (sialic acid) in multiple tissues, including the central nervous system, heart, muscles, and lymphocytes.[2] While the presence of rare cytoplasmic vacuoles in lymphocytes is not specific, their increased number and the context of suggestive clinical history may help narrow the differential diagnosis. Similar vacuoles in the cytoplasm of lymphocytes may also be seen in ceroid lipofuscinoses (Batten's disease), other lipid storage diseases (e.g., Wolman's disease), glycogen storage diseases (e.g., Pompe's disease), and mucopolysaccharidoses (e.g., Hurler's syndrome).[3] A specific diagnosis relies on biochemical and/or genetic testing.[4]

Conclusion

This is an image-based clinical vignette that demonstrates unusual cytoplasmic vacuoles in the lymphocytes in a stained peripheral blood smear from a 6-month-old infant who presented with seizures, hypotonia, and hepatosplenomegaly and was found to have the extremely rare lysosomal disorder, sialic acid storage disease. Although not specific, it is important to recognize this morphologic finding for reflex biochemical and genetic testing.

Conflict of Interest

None declared.

Authors' Contributions

S.B.K. made the diagnosis, wrote the first draft, and prepared the composite photograph. S.S. performed the literature search and edited the manuscript.

Compliance with Ethical Principles

No ethical concerns.

• References

• 1 Burlina AP, Manara R, Gueraldi D. Lysosomal storage diseases. Handb Clin Neurol 2024; 204: 147-172
• 2 Huizing M, Hackbarth ME, Adams DR. et al; FSASD Consortium. Free sialic acid storage disorder: progress and promise. Neurosci Lett 2021; 755: 135896
• 3 Goebel HH, Müller HD. Storage diseases: diagnostic position. Ultrastruct Pathol 2013; 37 (01) 19-22
• 4 Adams D, Wasserstein M. Free sialic acid storage disorders. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Amemiya A. eds. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993. –2024

Publication History

Article published online:
30 January 2025