Background: Proprotein convertase 1/3 (PC1/3) deficiency, an autosomal-recessive disorder caused by rare mutations in the proprotein convertase subtilisin/kexin type 1 (PCSK1) gene, has been associated with severe malabsorptive diarrhea and certain endocrine abnormalities.
Objective and hypotheses: To date, only 13 subjects with PC1/3 deficiency have been reported, now we want to report a new patient who was diagnosed PC1/3 deficiency with novel PCSK1 mutation and diabetes insipidus.
Method: A 3-month-old girl was referred to our clinic for the investigation of severe intractable diarrhea. She was the first child of non-consanguineous parents. She suffered from watery diarrhea started on the nineth postnatal day and persisted despite oral feeding with a variety of whole protein, hydrolysate, and amino acid-based infant formula feeds There was no improvement on a therapeutic trial of pankreatic enzyme supplements.
Results: She required long-term parenteral nutrition while establishing her on a hydrolyzed feed. She also had hypernatremic dehydration and polyuria at the presentation. Urine density was low and diabetes insipidus was diagnosed by DDAVP test. Serum levels of corticotropine, cortisol, GH, and free thyroxine were normal, proinsulin was high (81.07 pmol/l). We clinically diagnosed of the patient as PC1/3 deficiency and confirmed the diagnosis by demontration of a novel homozygous PCSK1 mutation.
Conclusion: PC1/3 is expressed richly in endocrine cells in the gut, in the arcuate and paraventricular nuclei of the hypothalamus, and β cells of the pancreas, where it has a well-defined role in processing proinsulin. Diabetes insipidus was also reported the previous eight patients. PC1/3 deficiency should be considered in patients presenting with intractable neonatal onset diarrhea and endocrinopathy like diabetes insipidus. Our case extends the clinical and molecular spectrum of human congenital PC1/3 deficiency.
20 - 22 Sep 2014
European Society for Paediatric Endocrinology