Primary intestinal lymphangiectasia (PIL) is a rare protein losing enteropathy characterized by a congenital malformation of lymphatic vessels in the small intestine, which results in poor lymphatic drainage and ultimately loss of lymphatic fluid into the small bowel lumen (1).
Tuberous sclerosis complex (TSC) is an autosomal dominant genetic condition that is characterized by benign hamartomatous growths, which can affect any organ system. A mutation in either the TSC1 (hamartin) or TSC2 (tuberin) genes can be identified in 75% to 90% of individuals who fulfill the criteria for the clinical diagnosis of TSC (2). Individuals with a pathogenic TSC2 variant present with a more severe phenotype than those with TSC1 mutations (3).
TSC has been reported in association with PIL in only 1 previous individual (4), a child with a TSC2 mutation. This child developed PIL symptoms during the first year of life, after a formal diagnosis of TSC at 2 months of age. To our knowledge we report only the second case of concurrent TSC and PIL, in particular this is the first where the TSC diagnosis was made subsequent to that of PIL.
Our patient was a 5-week-old boy who presented with right lower limb swelling secondary to lymphoedema, abdominal distension, and hypoalbuminemia in the setting of poor feeding and slow weight gain. He was born via a normal delivery at term gestation following an uncomplicated pregnancy. There was no significant family history.
PIL was confirmed at 8 weeks of age via an intestinal biopsy that revealed dilated lymphatic vessels within the lamina propria. The patient was managed with low long-chain triglyceride and high medium-chain triglyceride formula and regular albumin infusions, with improvement in clinical symptomatology and serum albumin.
Our patient developed seizures at 16 months of age. Brain magnetic resonance imaging demonstrated a moderate tuber load throughout multiple cerebral lobes and scattered subependymal nodules, consistent with TSC (see Fig. 1). Genetic testing identified a variant in the TSC1 gene (c.1498C>T;p.Arg500Ter), which has been previously reported as pathogenic (5).
Lymphatic malformations in TSC are well described, and there is a plausible pathophysiological connection between the lymphatic system and the mammalian target of rapamycin pathway, as hamartin and tuberin are key regulators of the mammalian target of rapamycin signaling pathway.
In conclusion, we report a second child with TSC and PIL. Clinicians should be aware of the possible relationship between the 2 conditions and consider an underlying diagnosis of TSC when presented with a patient with PIL.
The authors wish to acknowledge Associate Professor Susan M. White for her remarks regarding technical editing of the manuscript.
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5. Van Slegtenhorst M, Verhoef S, Tempelaars A, et al. Mutational spectrum of the TSC1 gene in a cohort of 225 tuberous sclerosis complex patients: no evidence for genotype-phenotype correlation. J Med Genet