title: Primary intestinal lymphangiectasia treated with rapamycin in a child with tuberous sclerosis complex (TSC).
abstract: Primary intestinal lymphangiectasia (PIL) is a rare protein-losing enteropathy characterized by a congenital malformation of the lymphatic vessels of the small intestine causing insufficient drainage and leakage of lymph fluid. Tuberous sclerosis complex (TSC) is an autosomal dominant genetic disorder characterized by benign hamartomas in multiple organ systems. While the lymphatic system has been implicated in TSC through lymphangioleiomyomatosis (LAM) and lymphedema, this paper reports the first case of PIL in TSC, a female patient with a TSC2 mutation. She developed persistent and significant abdominal distension with chronic diarrhea during her first year of life. Due to lack of treatment options and the involvement of the mTOR pathway in TSC, a trial of an mTOR inhibitor, rapamycin, was initiated. This treatment was highly effective, with improvement in clinical symptoms of PIL as well as abnormal laboratory values including VEGF-C, which was elevated to over seven times the normal upper limit before treatment. This case suggests that PIL is a rare manifestation of TSC, warranting the use of mTOR inhibitors in future studies.
authors.affiliation: Department of Neurology, Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Sarah F
authors.initials: SF
authors.lastname: Pollack
authors.affiliation: Department of Neurology, Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Alexandra L
authors.initials: AL
authors.lastname: Geffrey
authors.affiliation: Department of Neurology, Herscot Center for Tuberous Sclerosis Complex, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Thiele
authors.affiliation: Department of Pediatric Gastroenterology, Hepatology and Nutrition, Massachusetts General Hospital, Boston, Massachusetts.
authors.forename: Uzma
authors.initials: U
authors.lastname: Shah
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D008201:Lymphangiectasis, Intestinal / Q000188:drug therapy* / Q000235:genetics*; D008209:Lymphedema / Q000188:drug therapy* / Q000235:genetics*; D009154:Mutation / Q000235:genetics; D020123:Sirolimus / Q000627:therapeutic use*; D014402:Tuberous Sclerosis / Q000235:genetics*; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics; D055815:Young Adult
chemical_list: C000624653:TSC2 protein, human; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins; D020123:Sirolimus
keywords: mTOR; primary intestinal lymphangiectasia (PIL); rapamycin; tuberous sclerosis complex (TSC)