Desquamative enteropathy and pyloric atresia without skin disease caused by a novel intracellular beta4 integrin mutation.

[junctional epidermolysis bullosa]

Mutations in alpha 6 or beta 4 integrins (ITGA 6 , ITGB 4 ) are known to cause junctional epidermolysis bullosa with pyloric atresia (JEB-PA ), often lethal in infancy through skin desquamation . There is 1 report of pyloric atresia associated with a desquamatory enteropathy but without skin disease , of unknown molecular basis .We report 2 Kuwaiti siblings with pyloric atresia and life-threatening intestinal desquamation without significant skin abnormality . The older sibling died of intractable diarrhoea , and the younger sibling suffered episodes of massive protein-losing enteropathy , triggered by viral infections , in addition to obstructive uropathy . Mutation analysis was performed for ITGA 6 and ITGB 4 and expression of ITGA 6 and ITGB 4 protein was examined in skin and intestinal biopsies . Her serum also was incubated with normal intestine .We identified a novel mutation in ITGB 4 , with homozygous deletion of a single residue (isoleucine 1314 ) within the intracellular plectin -binding domain . Expression of ITGA 6 and ITGB 4 within skin , duodenal , and colonic epithelium was normal or minimally reduced , in contrast to previous reports . Biopsies taken during relapse showed accumulation of immunoglobulin G and C 1 q within intestinal basement membrane , whereas immunoglobulin G from her serum bound to basement membrane of normal small intestine . Immunomodulatory therapy induced significant improvement following relapses .I TGB 4 mutation may induce a desquamative enteropathy in infancy without significant skin disease . A history of pyloric atresia is important in infants with severe chronic diarrhoeal disease and should prompt investigation for JEB-PA associated mutations . Acquired immune responses may exacerbate primary genetic disorders of epithelial adhesion and immunomodulatory therapy may be beneficial .

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Diseases presenting "acquired immune responses may exacerbate primary genetic disorders" symptom

junctional epidermolysis bullosa

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