GP248 Mesenchymal stem cell therapy in microvillus inclusion disease. (June 2019)

• Record Type: Journal Article
• Authors: Onay, Ozge Surmeli; Tekin, Ayse Neslihan; Gunes, Damla; Aydemir, Ozge; Artan, Sevilhan; Aydemir, Yusuf
• Is Part Of: Archives of disease in childhood. Volume 104:(2019)Supplement 3
• Page Start: A133
• Page End: A133
• Publication Date: 2019-06
• Subjects: Children -- Diseases -- Periodicals; Infants -- Diseases -- Periodicals; 618.920005
• DOI: 10.1136/archdischild-2019-epa.307
• Languages: English
• ISSNs: 0003-9888

Abstract

Abstract : Objective: Microvillus inclusion disease (MVID; MIM #251850), is a rare life-threatening secretory and malabsorptive diarrhea of infancy due to mutations in the Myosin 5B (MYO5B) gene. Most of the patients die before achieving the opportunity of bowel transplantation due to electrolytes and renal tubular function disturbances and complications of parenteral nutrition. In this case report, results of stem cell therapy in a newborn infant with MVID were presented and discussed with the relevant literature. Case report: A 6-day-old male patient was referred to our NICU for profuse diarrhea beginning on the postnatal 2nd day after birth, metabolic acidosis and hyponatremia. He was born at 36 +4 gestational weeks as the fourth child of nonconsanguineous parents. Second and third siblings died at 2 and 3, 5 months due to complications of intractable diarrhea. Third child's exom sequencing identified a homozygous, disease-causing nonsense variant C.4399C> T (p.Gin1467*) in the MYO5B gene. Both parents were heterozygous for the mutation and they did not accept prenatal diagnosis. Our patient was also affected by homozygous mutation in MYO5B gene. With the knowledge of past history, total parenteral nutrition was started and maximum effort was directed to maintain fluid and electrolyte equilibrium. Patient had high fluid (350 ml/kg/day), sodium (20–25 meq/kg/day) and bicarbonate requirements (12–18 meq/kg/day). On 110 th day of life mesenchymal stem cells (1x10 6 Ü transduodenal and 2x10 6 Ü IV) were administered. Although fluid and electrolyte requirements did not decrease after 2 months of follow up after stem cell therapy, the rate of blood stream infections was reduced. Discussion and Conclusion: In MVID, mutations in the MYO5B gene which encodes a protein called myosin Vb contribute to the dysfunction of enterocytes. Survival rate is less than 25% at the age of 9 months. Mortality rate is also high after bowel transplantation. Recently, stem cell therapy was presented as a promising alternative strategy for overcoming the current limitations of intestinal failure treatment. We concluded that, the reason why our patient did not benefit from the treatment was rapid turnover of the intestine epithelial cells and the lack of receptive surface caused by the genetic defect. Furthermore, using modified intestinal stem cells instead of mesenchymal stem cells may be more beneficial. In our patient, decreased incidence of infection with probable immunomodulatory effects of stem cells was the secondary gain.