Primary intestinal lymphangiectasia (PIL, also referred to as Waldmann’s disease) is a rare disorder characterized by the dilation of intestinal lymphatic vessels, resulting in lymph loss. We present the case of a previously healthy eleven-year-old male, referred to immunology after recurrent Cryptosporidium infections, raising concerns about primary or secondary immunodeficiency. Clinical immunophenotyping revealed combined immunodeficiency, with severe hypogammaglobulinemia (total IgG: 212 mg/dL) and T cell lymphopenia (CD4+ count: 172 cells/µL; CD8+ count: 208 cells/µL). Clinical symptoms included peripheral edema, fatigue, chronic diarrhea, bloating, and abdominal pain. Extensive genetic testing, including a primary immunodeficiency panel and research-based whole-exome sequencing, did not identify a plausible causative variant. After initiating treatment with subcutaneous immunoglobulin and trimethoprim/sulfamethoxazole prophylaxis, immune parameters remained suboptimal (total IgG: 515 mg/dL; CD4+ count: 150 cells/µL; CD8+ count: 153 cells/µL). Stool samples collected by the patient’s gastroenterologist for persistent abdominal symptoms showed intestinal inflammation and suspected protein-losing enteropathy. The diagnosis of PIL was confirmed via esophagogastroduodenoscopy with biopsies. Dietary strategies were implemented, consisting of a low-fat diet (12 g/day), high-protein intake (75–125 g/day), and supplementation with ADEK vitamins and medium-chain triglyceride oil. This intervention resulted in improvement in antibody levels, with total IgG levels rising to 1114 mg/dL, although T cell lymphopenia remained at similar levels. In this report, we discuss the clinical course of this patient and provide an overview of the published literature regarding clinical manifestations and diagnostic laboratory values of immunodeficiency associated with PIL. We conclude that PIL should be considered as a cause of combined immunodeficiency or hypogammaglobulinemia in the absence of an alternative explanation in both adult and pediatric patients.
