Gastritis, Familial Giant Hypertrophic

Clinical Features

Giant hypertrophic gastritis was described as a clinical entity by Menetrier (1888). It is characterized by enlargement of the gastric mucosal folds, affecting primarily the body of the stomach with frequent sparing of the gastric antrum. Histologically, there is proliferation of the gastric glands with preservation of nuclear polarity, and cystic dilatation of the basilar portion of the glands. Hypochlorhydria and hypoproteinemia may be present. Larsen et al. (1987) stated that about 200 adult cases and a few childhood cases had been published. Familial occurrence was rare and had been reported only in sibs; there were 3 such instances. Lam et al. (1983) described 2 Chinese brothers, aged 27 and 29 years, with pachydermoperiostosis (167100) and Menetrier disease. Larsen et al. (1987) described Menetrier disease in a 49-year-old woman, in her son who had trouble beginning at age 16 years, and in the eldest daughter of this son who came to medical attention at age 5 years.

Marcus and Verp (1993) described a case of early-onset Menetrier disease in the son of Jordanian double-first-cousin parents. They suggested that the early-onset form may be inherited as a recessive. Manifestations became evident at 2 months of age; the boy died at age 10 months.

Coffey et al. (2007) reviewed the clinical features of Menetrier disease and gastrointestinal stromal tumors (GIST; 606764), both of which are hyperproliferative disorders of the stomach caused by dysregulated receptor tyrosine kinases (RTKs).

Pathogenesis

Coffey et al. (2007) reviewed the pathogenesis of Menetrier disease. Menetrier disease results from overexpression of TGFA (190170), a ligand for the RTK EGFR (131550), resulting in selective expansion of surface mucous cells in the body and fundus of the stomach. TGFA is not overexpressed elsewhere in the bodies of individuals with Menetrier disease. Pediatric forms of Menetrier disease are associated with cytomegalovirus (CMV) infection, and evidence suggests that the primary envelope glycoprotein of CMV, glycoprotein B (gB), may interact with EGFR.

Clinical Management

In a review, Coffey et al. (2007) stated that monoclonal antibodies targeting EGFR are effective in treating Menetrier disease.

Animal Model

Slappendel et al. (1994) described an autosomal recessive syndrome in dogs in which hypertrophic gastritis resembling Menetrier disease in man was associated with stomatocytosis (cup- or bowl-shaped red blood cells). The dogs had chronic hemolytic anemia. Slappendel et al. (1994) suggested that the disorder is due to abnormal lipid metabolism and that the stomatocytosis is not necessarily due to an intrinsic structural defect of the RBC membrane but may be induced by abnormal composition of the plasma.

In a review, Coffey et al. (2007) stated that metallothionein (see 156350)-Tgfa transgenic mice, which overexpress Tgfa in gastric mucosa, exhibit features characteristic of Menetrier disease on certain backgrounds.