Severe Combined Immunodeficiency: Improved survival leading to detection of underlying liver disease

Abstract

Abstract Background Adenosine deaminase deficiency (ADA) is a primary autosomal recessive genetic disorder leading to severe combined immunodeficiency (SCID). It is characterized pathophysiologically by intracellular accumulation of toxic products affecting lymphocytes and other organ systems. This cross sectional study was conducted to describe the liver disease in a cohort of patients with autosomal recessive ADA-SCID. Methods A single center cross sectional retrospective analysis (2006 to 2019) was performed in 18 patients with genetically confirmed ADA-SCID. Liver disease was defined as ≥1.5x the gender specific upper limit of normal (ULN; 33 IU/L for males and 25 IU/L for females) or moderate and severe increase in liver echogenicity on ultrasound. Results The cohort included 11 males, the median age was 11.5 (3.5–30.0 years) and median BMI was 18.4 kg/m2. Eighteen (100%), Seven (38%) and five (27%) patients had enzyme replacement therapy (ERT), gene therapy (GT) and hematopoietic stem cell transplant (HSCT). Five (?%) patients had ALT levels more than 1.5x the ULN. Liver echogenicity was increased mildly in 6 (33%), moderately in 2 (11%), severely in 2 (11%) and normal in 8 (44.4%) patients. All patients had normal FIB-4 and NAFLD fibrosis score indicating absence of advanced fibrosis in our cohort. Of 8 patients who had liver biopsies for diagnostic purposes, steatohepatitis measured by histopathology NASH-CRN scoring was noted in 4 patients. Discussion Non-immunologic manifestations of ADA-SCID have become more apparent in recent years as survival improved. In our cohort, the most common liver disease manifestation was steatosis. We postulate that hepatic steatosis noted is possibly multifactorial - recurrent infection, exposure to multiple medications and increased BMI.