Multivisceral Transplantation in Martinez-Frias Syndrome

Abstract

Aim: Martinez-Frías Syndrome (MFS) is a very rare condition with autosomal recessive inheritance, firstly described in 1992. The most frequent patterns are hypoplastic pancreas, intestinal atresia and gallbladder aplasia/hipoplasia, probably due to a midline disorder affecting the development of the duodenal-biliary-pancreatic junction. Esophageal atresia and/or neonatal diabetes can be associated. There are few cases described in the literature, all with poor prognosis, mainly due to the progression of the liver disease. We present one girl with this condition who was succesfully transplanted. Case report: Female neonatal infant weighing 2200 g, 35 weeks of gestational age, with intrauterine growth retardation, and Spanish consanguineous gypsy parents. Physical examination did not show external abnormalities. A laparotomy due to intestinal obstruction was necessary within the first 24 hours of life, revealing duodenal atresia, intestinal malrotation type I, and gallbladder agenesia. Although surgery was uneventful, she developed refractory diabetes and pancreatic exocrine insufficiency, requiring parenteral nutrition for months with growth delay and multiple sepsis due to central line infections (12 episodes). The genetic study showed a mutation on 16q22.1 involving the gene RFX6. She was listed for multivisceral transplant, and was transplanted at 15 months of age, with no major postoperative complications. Her native spleen was preserved, and colon was included in the graft. The enterectomy revealed a patched substitution of the intestinal mucosa by gastric mucosa, and pancreatic hypoplasia with absence of islets and few neuroendocrine cells. Induction protocol consisted of Basiliximab, Tacrolimus with steroids were given for maintenance. Due to renal insufficiency and hypertension, conversion to Sirolimus was decided one year after transplantation, first combined with Tacrolimus, and later as monotherapy. After more than 5 years since transplant, the patient has not suffered any rejection, GVHD or PTLD episode. She is 6 yo, off parenteral nutrition, has a normal diet, with one bowel movement/day, with no malabsorption, just mild iron deficiency and enjoys a normal life. Conclusion: This is the longest survivor with MFS described in the literature. Multivisceral transplantation seems to be an available option for these children although future will determine if the disease is totally cured.FigureFigure