Acknowledgement of Congenital Microvillus Atrophy has not been added yet.

Congenital Microvillus Atrophy is an ultra-rare disorder, with fewer than 100 cases documented worldwide. It is particularly notable in certain populations, including the Navajo community in Northern Arizona, where it has been reported at a higher incidence of approximately 1 in 12,000 live births. The condition affects more females than males, with a sex ratio of about 2:1.

 

Name	Abbreviation
Microvillus Inclusion Disease	MVID
Congenital Microvillus Inclusion Disease	CMID
Microvillus Atrophy	MVA
Davidson Disease
Congenital Familial Protracted Diarrhea Syndrome
Familial Enteropathy, Microvillus Syndrome
Intractable Diarrhea of Infancy

Congenital Microvillus Atrophy is primarily inherited in an autosomal recessive manner, meaning that both copies of the affected gene must have mutations for the disease to manifest (see RareShare Guide on Genetic Inheritance). The most commonly implicated genes include:

• MYO5B (Myosin 5b): This gene plays a role in the movement and anchoring of microvilli in intestinal epithelial cells. It encodes instructions for the protein myosin Vb, which is responsible for distributing elements within cells to their proper location. Mutations in MYO5B disrupt the normal function and location of microvilli on the exterior of the cell, leading to malabsorption problems.

• STX3 (Syntaxin 3) and STXBP2 (Syntaxin BP2): Genes involved in vesicle fusion and protein trafficking in intestinal cells. Mutations can impair the formation of the brush border intestinal lining and affect nutrient absorption.

• VTI1A (Vesicle Transport through Interaction with t-SNAREs Homolog 1A): Mutations in this gene also lead to defects in cellular processes crucial for maintaining microvillus integrity.

These mutations disrupt the normal assembly and function of the brush-border lining the small intestine, causing a failure of nutrient absorption and leading to the severe symptoms of CMA.

 

Hallmark features of Congenital Microvillus Atrophy appear in infancy and can be severe and life-threatening. Common symptoms include:

• Severe Diarrhea: Profuse, watery diarrhea that typically starts within hours or days of birth.

• Failure to Thrive: Inadequate growth and weight gain due to malabsorption of nutrients, despite normal or increased caloric intake.

• Chronic Dehydration: Persistent fluid loss due to diarrhea.

• Electrolyte Disturbances: Abnormal levels of sodium, potassium and chloride in the blood due to fluid loss.

• Hypoalbuminemia: Low levels of albumin in the blood resulting from protein malabsorption.

• Metabolic Acidosis: Acid build-up resulting from poor absorption of bicarbonate and other metabolic disturbances.

• Malnutrition: Progressive worsening of nutritional status and deficiencies in essential nutrients, especially fat-soluble vitamins (A, D, E, K).

• Vomiting: Often accompanies gastrointestinal distress.

In the most severe cases, if left untreated, infants with CMA may experience intestinal failure, which can be fatal without specialized intervention. In the late onset form occurring in the first few months of life, symptoms are less severe with progressive weight loss, growth retardation and malnutrition becoming apparent.

Diagnosis of Congenital Microvillus Atrophy is based largely on clinical presentation and may include:

1. Clinical History: A detailed history of symptoms such as severe diarrhea, failure to thrive and dehydration, typically beginning in the neonatal period.

2. Fecal Electrolyte Analysis: Elevated fecal sodium or chloride levels may be indicative of secretory diarrhea.

3. Histopathological Examination:

   • Light Microscopy: May show flattened villi and deterioration of the intestinal wall.

   • Electron Microscopy: Characteristic findings include the absence or gross abnormalities of microvilli and the presence of microvillus inclusions, which are intracellular vesicular structures.

4. Genetic Testing: Molecular analysis can confirm mutations in the MYO5B, STX3, STXBP2 or VTI1A genes, providing a definitive diagnosis.

5. Nutritional Assessments: Blood tests to identify deficiencies in electrolytes, proteins (such as albumin) and fat-soluble vitamins.

Diagnostic tests of Congenital Microvillus Atrophy has not been added yet

There is no cure for Congenital Microvillus Atrophy, so treatment is focused on providing nutrients, managing symptoms and preventing complications. The ongoing care goal is to maintain and promote growth and development as much as possible. Key treatment approaches include:

• Parenteral Nutrition (PN): Intravenous feeding may be necessary to provide nutrients and hydration when enteral feeding is not sufficient due to malabsorption.

• Enteral Nutrition: Specialized enteral feeds may be used, but absorption may remain impaired.

• Electrolyte and Fluid Management: Correction of dehydration and electrolyte imbalances is crucial.

• Vitamin Supplementation: Fat-soluble vitamins (A, D, E, K) should be supplemented, as they are often poorly absorbed.

• Small Bowel Transplantation: In cases of severe intestinal failure that cannot be managed with nutrition, small bowel transplantation may be the only definitive treatment. This procedure offers the possibility of improved survival and quality of life but is not without risks.

• Symptom Management: Some patients may benefit from treatments like intravenous Octreotide to manage diarrhea and reduce gastrointestinal secretions.

The prognosis for Congenital Microvillus Atrophy is generally poor without prompt and ongoing medical intervention. Without parenteral nutrition and other supportive measures, most infants with this condition do not survive beyond infancy due to complications such as malnutrition, dehydration and electrolyte imbalances. However, with early and aggressive management, including parenteral nutrition, some children may survive into childhood and even adulthood, although they may continue to experience chronic nutritional issues.

Small bowel transplantation can improve the prognosis in patients who develop intestinal failure, but it remains a complex procedure with risks of rejection and long-term complications. Long-term survival rates post-transplantation are variable and still require more data to determine the overall success

Tips or Suggestions of Congenital Microvillus Atrophy has not been added yet.

1. van der Velde, K.J., et al. (2013). “An Overview and Online Registry of Microvillus Inclusion Disease Patients and their MYO5B Mutations.” Human Mutation, 34(12), 1597-1605.

2. Orphanet: Microvillus inclusion disease. (2017). Orpha.net. https://www.orpha.net/en/disease/detail/2290?name=Congenital%20Microvillus%20Atrophy&mode=name.

3. Microvillus Inclusion Disease. (2023, November 20). National Organization for Rare Disorders. https://rarediseases.org/rare-diseases/microvillus-inclusion-disease/.

4. https://medlineplus.gov/genetics/condition/microvillus-inclusion-disease/#causes