A case of autoimmune lymphoproliferative syndrome in pregnancy

Case Report
Autoimmune lymphoproliferative syndrome (ALPS) is a rare genetic disorder caused by mutations in the FAS pathway, resulting in impaired lymphocytic apoptosis. Clinical manifestations include chronic lymphoproliferation and elevation in double negative T-cells (DNT), which express the alpha beta T-cell receptor but lack CD4 and CD8 expression. We present a case of ALPS in pregnancy, offering crucial clinical insights into this unique patient population, given limited existing reports.
A 39-year-old gravid female presented to hematology for management of ALPS in pregnancy. Her medical history was notable for autoimmune hemolytic anemia at age 6 requiring splenectomy at age 9. She remained clinically stable thereafter without further treatment. Similar presentation in niece prompted genetic evaluation for an underlying familial ALPS. Genetic testing revealed a heterozygous FAS c.718 A>G mutation. Peripheral blood flow cytometry demonstrated characteristic DNT cells, and in the context of her known autoimmune hemolytic anemia, these findings established the diagnosis of ALPS. She did not have any clinical manifestations of the disease at time of conception and did not require immunosuppressive therapy. Laboratory findings were significant for long-term thrombocytosis as a sequela of splenectomy. She had an uneventful pregnancy with close multidisciplinary monitoring and underwent caesarian section at full-term without complications. She completed 6 weeks of low-molecular weight heparin post-partum for thromboembolism prophylaxis.
Pregnancy in individuals with ALPS is considered high risk due to the potential for disease exacerbation, increased infection risk, and adverse maternal/fetal outcomes. Existing literature regarding the role of FAS ligand expression in maintenance of pregnancy and immune support at maternal-fetal interface suggests possible risk of pre-term complications in these patients; therefore, enhancing significance of reporting our patient. A case report by Patti et al. describes a full-term, uneventful pregnancy in a patient whose ALPS was well-controlled with immunosuppressive medication suggesting that well-controlled disease before and during gestation is a favorable factor. This highlights the importance of close multidisciplinary monitoring and use of pregnancy-safe immunosuppression to optimize maternal and fetal outcomes. Given the autosomal inheritance pattern of ALPS, preconception counseling is essential. Although our patient remained asymptomatic throughout her pregnancy, close monitoring of the neonate is warranted to detect potential complications and evaluate for inheritance of the FAS mutation. ALPS in pregnancy presents unique maternal and fetal risks, necessitating careful, multidisciplinary management. Collaboration among obstetrics, hematology, and when appropriate, rheumatology is crucial to ensure timely intervention and to optimize outcomes for both mother and child.