Intractable Neonatal Diarrhea Related to a New Homozygous Pathogenic Variant of PCSK1 Gene

background: proprotein convertase 1/3 (PC1/3) deficiency (OMIM: 600955) is a very rare disease characterized by severe intractable diarrhea in the first years of life, followed by obesity and several hormonal deficiencies later in life. Early in life, almost all the neonates will have significant risk of mortality and failure to thrive secondary to severe generalized malabsorptive diarrhea, dehydration and metabolic acidosis.

Objective: To report 2 siblings with a new PCSK1 gene mutation

the 2 siblings were born term. they are products of consanguinous marriage. the 1st baby boy was admitted multiple times for severe diarrhea that started in the first month of life, hypernatremic dehydration and metabolic acidosis. The diarrhea resisted to all formula milk changes The baby was dependant of total parenteral nutrition witch stopped the diarrhea and leaded to an appropriate weight gain. Long term TPN couln’t be offered to him for social reason and he died at 8 months from sepsis and denutrition. The whole exom sequencing revealed a PCSK1 variant c.641dup p.(Glu215Argfs*8) in homozygous state. His younger sister developed diarrhea at 5 days of life that was less severe than her brother but with inappropriate weight gain. The same gene mutation was found.

Conclusion: Tthe causes of intractable neonatal diarrhea are various and the classic gastro intestinal investigations are fastidious. WES allows the diagnosis of a very rare disease in this family.