Trehalase Deficiency

A number sign (#) is used with this entry because of evidence that trehalase deficiency is caused by homozygous mutation in the trehalase gene (TREH; 275360) on chromosome 11q23.

Description

Trehalose is a disaccharide found in mushrooms, algae, and insect hemolymph; mushrooms and products containing baker's yeast are thus the only sources of trehalose in the human diet. The high concentration of trehalose in cryptobiotic plants is responsible for their remarkable ability to go through cycles of desiccation and rehydration without injury. This led to interest by the food industry in the addition of trehalose to foodstuffs to improve the longevity and quality of dried food. However, ingestion of a disaccharide in an individual who cannot digest it results in osmotic diarrhea, abdominal pain, and increased rectal flatulence (summary by Murray et al., 2000). Isolated trehalose intolerance due to deficiency of trehalase (TREH; 275360) is probably rare in adult white Americans (Welsh et al., 1978), but has been estimated at 8% in Greenlanders (Gudmand-Hoyer et al., 1988).

Clinical Features

Madzarovova-Nohejlova (1973) reported a family in which a 24-year-old presented with diarrhea and vomiting after ingestion of a large amount of edible mushrooms. Peroral biopsies of jejunal mucosa in 6 members of the family revealed trehalase deficiency in the patient and his father, and both showed trehalose malabsorption on oral tolerance test. An uncle and 2 cousins with a history of mushroom intolerance were not available for study. Madzarovova-Nohejlova (1973) stated that young mushrooms are the only known dietary source of trehalose for humans, noting that trehalose is hydrolyzed to glucose as mushrooms age.

Gudmand-Hoyer et al. (1988) analyzed trehalase activity in jejunal biopsy specimens taken from 97 adult Greenlanders undergoing surgery for peptic ulcer or cancer of the stomach or pancreas. Trehalase activity ranged from nearly zero to 94 IU/g of protein; 8 patients had an activity of less than 6 IU/g, and 14 had an activity of less than 8 IU/g. Thus, Gudmand-Hoyer et al. (1988) estimated the incidence of trehalase deficiency in Greenlanders to be 8%, and stated that in their series of more than 500 Danish biopsy specimens, they had not found any trehalase deficiency. Gudmand-Hoyer et al. (1988) noted that the symptoms of trehalose malabsorption are the same as for other disaccharide malabsorption syndromes and stated that it undoubtedly has the same pathophysiologic mechanism: the nondigested disaccharide and its hydrolysates, caused by bacterial fermentation, exert a pronounced osmotic effect in the intestine, drawing water into it; the consequent accelerated intestinal passage of the intestinal contents results in diarrhea and diffuse abdominal symptoms.

Murray et al. (2000) performed histologic assessment and measured maltase, sucrase, lactase, and trehalase activities in endoscopic distal duodenal biopsies from 400 patients with suspected malabsorption. Normal duodenal histology was present in 369 of the patients, and the normal range of trehalase activity as measured in those individuals was 4.79 to 37.12 U/g protein. In patients with untreated celiac disease, trehalase activity was decreased but recovered to normal in most patients within 6 months of starting a gluten-free diet. Only 1 patient with normal histology had isolated low trehalase activity (4.48 U/g). Murray et al. (2000) concluded that the incidence of primary trehalase deficiency in the UK must be extremely low.

Molecular Genetics

To identify individuals carrying homozygous predicted loss-of-function (pLoF) mutations influencing more than 200 biochemical and disease traits, Saleheen et al. (2017) sequenced the protein-coding regions of 10,503 adult participants in the Pakistan Risk of Myocardial Infarction Study (PROMIS), designed to understand the determinants of cardiometabolic diseases in individuals from South Asia. They identified 49,138 rare (less than 1% minor allele frequency) pLoF mutations which were estimated to knock out 1,317 genes, each in at least 1 participant. Saleheen et al. (2017) identified 6 individuals who were homozygous for a splice acceptor site deletion (275360.0001) in the TREH gene. These individuals also had lower concentrations of several apolipoprotein B-containing lipoprotein subfractions. No phenotypic information specific to the homozygous individuals was provided.