Microvillus inclusion disease (ORPHA:2290)
Microvillus inclusion disease (MVID) is a very rare and severe intestinal disease characterized by intractable neonatal secretory diarrhea persisting at bowel rest and specific histological features of the intestinal epithelium.
Epidemiology
Prevalence data are not available. Less than 200 cases have been reported to date. There is a male predominance, with a sex ratio of 1.5:1.
Clinical description
Two clinical forms of MVID have been described: an early-onset form, developing within hours or days of birth, and a late-onset form, occurring in the first months of life. In both, intractable, watery diarrhea is profuse and leads to severe metabolic acidosis, dehydration, malabsorption and failure to thrive. Total parenteral nutrition is necessary, however, in some later-onset cases, partial oral absorption has been described. The intestinal insufficiency is progressively life-threatening in the absence of rapid, appropriate hydroelectrolytic and nutritional compensation. Developmental delays may be present and rare associated anomalies (e.g. inguinal hernia, renal dysplasia) have been reported. Long-term parenteral nutrition may be complicated with specific liver cholestasis. Atypical forms of MVID, without detectable microvillus inclusions and less severe course, have been described.
Etiology
MVID is caused by mutations in the MYO5B gene (18q) resulting in perturbation of intestinal epithelial cell apical polarity. Disorganized microvilli impair the absorptive capacity of the enterocytes. A variant of the disorder, without microvillous inclusion vesicles, is caused by loss-of-function mutations in the syntaxin 3 (STX3) gene (11q12.1), and when associated with hemophagocytic lymphohistiocytosis, can also be caused by mutation of STXBP2 (19p13.2) gene. Some patients do not display mutations in any identified gene.
Diagnostic methods
The diagnosis is suspected based on clinical manifestations and is confirmed by histological analysis of small bowel biopsies showing villous atrophy and abnormal periodic acid-Schiff stain (PAS)-positive inclusion material in intestinal epithelium, without crypt hyperplasia. Electronic microscopy reveals microvillous atrophy and in most cases, microvillous inclusion vesicles in the cytoplasm of enterocytes. Molecular genetic testing has become essential to confirm the diagnosis.
Differential diagnosis
The differential diagnosis includes rare congenital enteropathies such as autoimmune enteropathy, chloride diarrhea, congenital sodium diarrhea, and congenital tufting enteropathy.
Antenatal diagnosis
As MVID is a rare disease with no specific and systematic prenatal signs. Prenatal diagnosis is possible only if the specific gene mutation has been identified in an affected member of the family.
Genetic counseling
The inheritance pattern of MVID is autosomal recessive (parents of an affected individual have a probability of 25 % to transmit the causal mutation to their offspring). Genetic counseling should be offered to affected families in order to provide more information about this genetic condition, its risk of recurrence and the necessity/availability of prenatal diagnosis.
Management and treatment
To date, there is no curative therapy for MVID. Treatment involves total parenteral nutrition, intestinal transplantation (when long-term parenteral nutrition is no longer possible) and, when required, associated liver transplantation.
Prognosis
Due to the severity and precocity of the symptoms, as well as the long-term parenteral nutrition's complications, prognosis for MVID is generally poor. Causes of death include severe dehydration and metabolic imbalance, malnutrition, and sepsis.

                            Last update: 
                            October 2017


                            - Expert reviewer(s): 
                            Pr Olivier GOULET  - Dr Julie SALOMON