LAUSR

A healthy male teenager presented to his primary care paediatrician for a routine checkup including receipt of vaccines. On clinical examination, isolated splenomegaly was noted, a few days later confirmed by MRI (figure 1). Extensive investigations excluded an underlying oncological, infectious or metabolic disease. Due to bicytopenia (haemoglobin 69 g/L, white blood count 1.52×10/L, platelet count 151×10/L) with suspected autoimmune pathogenesis, extended immunological diagnostics were performed. This revealed an increased serum IgG concentration (19.3 g/L (5.9–12.5)) and an increase in doublenegative T cells (DNT) (14.7%, <6%) by flow cytometry of peripheral blood lymphocytes. In addition, serum vitamin B12 (1530 pg/mL (182–1090)) and soluble Fas ligand levels (2428 pg/mL, <250) were elevated. In view of these highly suggestive findings of autoimmune lymphoproliferative syndrome (ALPS), functional and genetic diagnostics were performed to confirm the suspected diagnosis. Genetic investigation revealed a previously unknown heterozygous variant in FAS (NM_000043.6:c.806A>T, p.Asp269Val, not present in gnomAD), which was functionally verified by defective in vitro lymphocyte apoptosis. Thus, ALPS was diagnosed according to current criteria (box 1). QUESTIONS 1. What causes ALPS? A. Chronic infection. B. Metabolic disorder. C. Immune disorder. 2. How can a clinical diagnosis of ALPS be confirmed? A. Combination of clinical features and a single blood test. B. Combination of clinical features and imaging. C. Combination of history, clinical features and several laboratory tests. 3. How is ALPS treated? A. Physical activity. B. Immunosuppression. C. Radiotherapy. 4. How is the prognosis of ALPS? A. Generally favourable, especially with appropriate treatment. B. Very poor, with drastically reduced life expectancy. C. Good, with no increased risk of cancer. Answers can be found on page 2. Figure 1 (A) Clinical presentation of splenomegaly. The colour painted on the skin indicates the caudal spleen border. (B) MRI findings (CUBE STIR (Short Tau Inversion Recovery) coronal, T2w axial with fat saturation) during diagnostic workup. The white lines indicate the size of the spleen in all three dimensions (20×13×7 cm, volume 1000 mL, 97.5th percentile=264.6 mL). Box 1 The clinical diagnosis of autoimmune lymphoproliferative syndrome can be made if at least one of the primary and one of the secondary diagnostic criteria are met (European Society for Immunodeficiencies registry working definition 2019)