Congenital Enteropeptidase Deficiency

By usmlevideoss

Introduction

  • Definition: Congenital enteropeptidase deficiency (also known as congenital enterokinase deficiency) is a rare autosomal recessive disorder.
  • Cause: Impaired protein digestion and absorption due to the absence or dysfunction of enteropeptidase, an enzyme produced by the duodenal mucosa.

Etiology

  • Genetic Cause: Mutations in the TMPRSS15 gene, which encodes enteropeptidase.
  • Inheritance Pattern: Autosomal recessive.

Epidemiology

  • Prevalence: Extremely rare, with only a few cases reported globally.
  • Predilection: No specific geographic or ethnic association.

Pathophysiology

  • Normal Function: Enteropeptidase, a duodenal brush-border enzyme, activates trypsinogen into trypsin.
  • Role of Trypsin:
    • Activates other pancreatic enzymes (e.g., chymotrypsin, elastase).
    • Digests proteins into amino acids and peptides.
  • Deficiency Consequences:
    • Malabsorption of proteins.
    • Protein-energy malnutrition.
    • Failure to thrive.

Clinical Manifestations

  • Onset: Symptoms typically appear in infancy.
  • Key Features:
    • Failure to thrive despite adequate caloric intake.
    • Chronic diarrhea (steatorrhea due to fat malabsorption).
    • Edema (caused by hypoalbuminemia).
    • Muscle wasting and poor weight gain.
    • Abdominal distension and irritability.

Diagnosis

  1. Clinical History and Symptoms:
    • Chronic diarrhea, malnutrition, and failure to thrive in infancy.
  2. Laboratory Findings:
    • Hypoalbuminemia and hypoproteinemia.
    • Normal pancreatic enzyme production with low activated enzyme activity.
  3. Stool Analysis:
    • Fat malabsorption (steatorrhea).
    • Presence of undigested proteins.
  4. Enzyme Assay:
    • Low or absent enteropeptidase activity in duodenal biopsies.
  5. Genetic Testing:
    • Mutation analysis of the TMPRSS15 gene.

Treatment

  • Dietary Modifications:
    • High-protein diet using hydrolyzed or predigested proteins (peptide-based or amino acid-based formulas).
    • Medium-chain triglycerides (MCTs) supplementation to manage fat malabsorption.
  • Enzyme Replacement Therapy:
    • Oral pancreatic enzyme supplements containing trypsin and other proteases.
  • Nutritional Support:
    • Caloric supplements and vitamins to combat malnutrition.

Prognosis

  • Early Diagnosis and Management:
    • Normal growth and development achievable.
  • Delayed Diagnosis:
    • Severe malnutrition and developmental delays may occur.

SUPERPoint

  • Congenital enteropeptidase deficiency causes severe protein malabsorption, manifesting as failure to thrive and chronic diarrhea in infancy. It requires enzyme supplementation and dietary modifications for effective management.

SUPERFormula

Patient presents with failure to thrive, chronic diarrhea, and hypoalbuminemia + Rare autosomal recessive disorder + Mutation in TMPRSS15 gene + Loss of trypsin activation leads to protein malabsorption + + Diagnosed by enzyme assay and genetic testing + Treated with enzyme supplements and hydrolyzed protein diets = Congenital Enteropeptidase Deficiency