Case presentation:

A 7-month-old Pakistan boy, the first child of a couple with close tie of consanguinity, was admitted to hospital because of fever and symptoms of upper respiratory tract infection. He was born at 36 weeks of gestation by emergency LSCS for the indication of suspected foetal distress, with a birth weight of 1.55 Kg. Physical examination revealed a small size baby with all the parameters below the 3rd percentile and also developmental delay, but no dysmorphic features. A complete blood count (CBC) showed Hb 14.6 g/dL, MCV 107 fL, MCH 37.0 pg, Platelet count 187 x 10⁹/L, WBC count 9.3 x 10⁹/L (D/C: Neutrophils 22%, Lymphocytes 69%, Monocytes 3%, Eosinophils 6%). Some cells of interest in the peripheral blood smears are shown in Figures 1a & 1b. What are these cells?

Futher laboratory investigations:

A MRI of the brain was normal. Acid hydrolases (lysosomal enzymes) was increased in the skin fibroblast culture fluid but decreased within the cells. The diagnosis was confirmed by demonstration of leucocyte G1cNAc-phosphotransferase deficiency.

Diagnosis:

I-cell disease (mucolipidosis II)

Subsequent course:

The patient received a peripheral stem cell transplant from his HLA-identical father at one year of age. Engraftment was attained at day 24. At day 172, mixed chimerism, viz. presence of both host and donor cells, was shown in the marrow by molecular studies. Leucocyte G1cNAc-phosphotransferase assay revealed a level consistent with carrier status.

Discussions:

Metabolic storage disorders posed difficulties in the diagnostic process to both the clinicians and the clinical laboratories. For the former, many of these disorders are rare and they may present similarly; and for the latter, the range of investigations and enzyme assays to reach the diagnosis are wide and these tests are costly, labour-intensive, time-consuming and not easily available.

Metabolic storage disorders are linked to haematology laboratories because some conditions have characteristic abnormalities which can be detected in a peripheral smear (Figure 1 & 2) or bone marrow aspirate.

The right place in a standard staining peripheral smear to look for vacuolated lymphocytes is the trails of the film where cells may be somewhat distorted and / or not well separated. This is the area easily ignored, but it is here that vacuolated lymphocytes are most abundant, and if present, are easily visible under a x 20 objective of a light microscope. Electron microscopy is not usually necessary, except in conditions that examination of the ultrastructures of the granules may give a clue to a specific diagnosis.

Vacuoles are vacuoles, i.e., they are well demarcated and clear, and present in many lymphocytes. The occasional tiny single "vacuole" present in the cytoplasm of one or two lymphocytes is always not significant. And vacuolated lymphocytes should not be confused with normal monocytes and vacuolated lymphoblasts (ALL FAB : L3).

According to Professor Brian Lake, there are two main categories of lymphocyte vacuolation:

1. Few small vacuoles in many lymphocytes;
2. Many larger vacuoles in many lymphocytes.

Under each of these 2 headings there is a list of differential diagnoses (Table 1). Therefore, examination of the presence of vacuolated lymphocytes and the size or appearance of the vacuoles can help to narrow down the scope of further investigations, or pinpoint certain specific diagnosis.