Tag Archives: protein losing enteropathy

DGAT1 Deficiency

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Briefly noted: JM van Rijn et al. Gastroenterol 2018; 155: 130-43.  This study of 10 patients from 6 families (5 had consanguinity) was the largest cohort to date describing the clinical features in this disorder and used patient-derived fibroblasts and organoids to understand the pathophysiology.

Key clinical features:

  • Early-onset vomiting and/or diarrhea
  • Protein-losing enteropathy/hypoalbuminemia

Key finding in study:

  • These patients had altered lipid metabolism and were susceptible to lipid induced cell death.  Thus DGAT1 mutations cause congenital diarrhea and this is linked to fat intolerance.

Related blog posts:

Sunshine Meadows, Banff Natl Park

CHAPLE Syndrome: Early-Onset Protein-Losing Enteropathy

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With more widespread use of whole exome sequencing, new diseases are being uncovered.  CHAPLE syndrome has recently been described: A Ozen et al. NEJM 2017; 377: 52-61.

CHAPLE syndrome comprises CD55 (decay-acclerating factor) deficiency with hyperactivation of complement, angiopathic thrombosis, and protein-losing enteropathy (PLE).

  • In this report of 11 patients, 8 presented before 2 years of life.
  • Disease manifestations included chronic diarrhea in 8, abdominal pain in 4, vomiting in 6.
  • PLE features included hypoalbuminemia in 10 of 11, hypogammaglobulinemia in all 11, and primary intestinal lymphangiectasia (or Waldmann’s disease) in 5.
  • Thrombotic disease: 3 with thrombosis, 2 with thrombocytosis
  • Endoscopic findings (2 patients did not have endoscopy): mucosal ulcer in 4, lymphoid infiltrates in mucosa in 6
  • Other features: recurrent lung infections in 5, hypothyroidism in 3, arthritis/arthralgia in 2, and clubbing in 5
  • Patents’ T lymphocytes showed increased complement activation; cytokine modulation by CD55 were defective
  • Treatment: Genetic reconstitution of CD55 or treatment with a complement-inhibitory therapeutic antibody reversed abnormal complement activation

In a related letter to the editor (NEJM 2017; 377: 87-9), Kurolap et al show that eculizimab therapy was helpful in a family with CHAPLE syndrome, reducing PLE and bowel movements within 100 days of initiation.

My take: CHAPLE syndrome needs to be considered in young patients with PLE (& primary intestinal lymphangiectasia).

Shem Creek, SC