The patient is a five-year-old fully immunized boy who presents for immunological investigation of inflammatory gastritis and enteritis. He was previously healthy until age three, when he presented to an outside facility with lower extremity edema and hypoalbuminemia. Endoscopy revealed gastritis and duodenitis with grossly normal esophagus and colon, resulting in a diagnosis of protein losing enteropathy. Elimination diet was attempted with variable adherence. He continued to follow in gastroenterology clinic with ongoing abdominal complaints including intermittent abdominal pain, abdominal distention, vomiting and alternating constipation and diarrhea without blood. At initial presentation, his weight was at 14% and height at 25%, but this has decreased over two years to weight < 1% and height < 5%. Additional past medical history is notable for a documented episode of transient left ankle swelling at age 44 months. There is no history of fevers, sinopulmonary infections, skin lesions, invasive bacterial infections, mucocutaneous candidiasis, recurrent viral infections or endocrine abnormalities. The family is of African-American and Congolese ancestry. The patient has no siblings, both parents are healthy and there is no family history of immune disorders, autoimmunity or inflammatory bowel disease. Additional studies revealed a normal white blood cell count with elevated monocytes, normal hemoglobin, platelets >1000 x 109 cells/L, persistent hypoalbuminemia (1.4-2.8 g/dL), elevated C-reactive protein (20-51 mg/L), intermittently elevated erythrocyte sedimentation rate (12-44 mm/h), negative tissue transglutaminase IgA and consistently elevated fecal calprotectin and alpha-1-antitrypsin. Initial immune evaluation had revealed normal dihydrorhodamine flow cytometry; elevated IgE (822) but normal IgM, IgA, IgG and IgD; and normal T, B and NK cell numbers (CD19+ 737 cells/μL, CD4+ 1441 cells/μL, CD8+ 376 cells/μL, CD16/56+ 390 cells/μL). Over the following two years, he underwent two additional esophagogastroduodenoscopies and colonoscopies, which have repeatedly shown ulcerations of the stomach and duodenum with normal esophagus and colon. Biopsies of the duodenum in at ages 3 and 4 showed duodenal mucosa with villous blunting, crypt hyperplasia, expansion of the lamina propria, neutrophilic inflammation, intact goblet and Paneth cells, detectable plasma cells and absent intraepithelial lymphocytosis. CT revealed hepatosplenomegaly. CT enterography revealed mild small bowel wall thickening and mucosal hyperenhancement. Based on clinical history and studies, very early onset inflammatory bowel disease was suspected. Enteral budesonide was attempted, but patient had difficulty with adherence. He completed a 5-week course of prednisolone with temporary improvement in symptoms but recurrence after steroids were tapered. Due to the concern for a genetic cause of early onset inflammatory bowel disease, whole exome sequencing was performed of proband and both parents. This revealed a paternally inherited heterozygous pathogenic mutation in mevalonate kinase (MVK; p.Y116H) and a maternally inherited variant of uncertain significance in Inducible T Cell Costimulator (ICOS; p.V151L). Additional functional testing is underway to understand whether this patient’s variants may play a role in disease pathogenesis or whether additional as-yet unidentified genetic variants may be responsible for his immune disorder.
|Original language||English (US)|
|Number of pages||163|
|State||Published - Apr 2020|
PubMed: MeSH publication types