Hereditary multiple intestinal atresia (HMIA) with severe combined immunodeficiency (SCID): a case report of two siblings and review of the literature on MIA, HMIA and HMIA with immunodeficiency over the last 50 years

Abstract

Hereditary multiple intestinal atresia (HMIA), a presumed autosomal recessive disorder, is an unusual and rare form of recurrent intestinal atresia which can be associated with severe combined immunodeficiency (SCID). The combination of HMIA and SCID is invariably lethal. The authors describe this fatal association in two siblings. The parents are consanguineous and have three other normal healthy children. Both index cases had abnormal antenatal ultrasounds and were symptomatic after birth. The final diagnosis of HMIA with SCID was confirmed in both siblings. They were never able to receive enteral feeds, remained totally dependent on parenteral nutrition, had repeated episodes of sepsis and died after a very difficult neonatal intensive care course. In this article we have reviewed the clinical course and outcome of both cases. The existing literature on multiple intestinal atresia, HMIA and HMIA with immunodeficiency is also reviewed.

Whole-exome sequencing identifies tetratricopeptide repeat domain 7A ( TTC7A ) mutations for combined immunodeficiency with intestinal atresias

“…10 Recurrence of cases in the same sibship 3, 6, 7, 11, 12 and parental consanguinity 5, 11, 13–15 have since been reported in several other families of various descent.…”

Genetics of gastrointestinal atresias

“…A non-hereditary form and an autosomal recessive hereditary form have been described. Moreover, MINAT is sometimes associated with either mild or severe combined immunodeficiency (SCID, MIM: 601457); this combination is invariably lethal (Ali et al, 2011;Shorter et al, 2006). Although the nonhereditary form is thought to derive from vascular disruption, there have been reports of non-hereditary cases, suggesting a hereditary form of MINAT is a consequence of a malformative process of the gastrointestinal tract rather than a vascular anomaly (Baglaj et al, 2008;Puri and Fujimoto, 1988).…”

Severe Combined Immunodeficiencies

“…447,448 The association of combined immunodeficiency with MIA (CID-MIA) was reported for the first time in 1990, when Moreno et al described three siblings with MIA associated with severe hypogammaglobulinemia and lymphopenia; one of these infants was shown to lack circulating T cells and hence was diagnosed with severe combined immune deficiency (SCID). 450,451 Although most cases of CID-MIA are sporadic, a genetic basis with autosomal recessive inheritance was postulated when five French-Canadian cases in three sibships with common ancestry (two of which also showed parental consanguinity) were described. 450,451 Although most cases of CID-MIA are sporadic, a genetic basis with autosomal recessive inheritance was postulated when five French-Canadian cases in three sibships with common ancestry (two of which also showed parental consanguinity) were described.…”

“…449 Profound immunological defects have since been reported in several other cases of patients with multiple intestinal atresias. 452 Since then, recurrence of cases in the same sibship 449,453 and parental consanguinity 451,454 have been reported in several other families of various descent. 452 Since then, recurrence of cases in the same sibship 449,453 and parental consanguinity 451,454 have been reported in several other families of various descent.…”

“…450,451,453 Moreover, fatal graft-versus-host disease (GvHD) following transfusion of unirradiated blood products 462,463 or combined liver and small bowel transplantation 463 has also been reported. 450,451,453 Moreover, fatal graft-versus-host disease (GvHD) following transfusion of unirradiated blood products 462,463 or combined liver and small bowel transplantation 463 has also been reported.…”