β6 integrinosis: a new lethal autosomal recessive ITGB6 disorder leading to impaired conformational transitions of the αVβ6 integrin receptor

We read with interest the recent work by Schleier et al 1 demonstrating consequences of impaired α4β7 integrin-dependent gut homing of intestinal macrophages on wound healing, which fits well with own observations we have made in a case of congenital infantile intractable diarrhoea linked to impaired integrin receptors in intestinal epithelia (αVβ6). Specifically, a male dizygotic twin was delivered dystrophic (1715 g) at 36 weeks of gestational age and developed intractable diarrhoea within the following 2 months, contrary to his twin brother. Severe systemic infection or parasitosis was ruled out, but subsequently low-serum IgG and severe neutropenia occurred due to consumption of neutrophils during the prolonged diarrhoea. Eventually, he developed cholestatic hepatopathy and thrombocytopenia and died of uncontrollable GI, dermal haemorrhages and hepatic failure at 7 months of age. Extensive diagnostics included biopsies of liver, muscle, bone marrow, small intestine, the exclusion of known congenital diarrhoea reasons and immunodeficiencies by leucocyte FACS, CD40L expression, WASP staining, et cetera with no results.2 Familial anamnesis revealed similar fatalities of a sister and further cousins from the patient’s …