WHEN LESS IS MORE: INSIGHTS INTO SODIUM AND PHOSPHATE HOMEOSTASIS FROM A MICROVILLUS INCLUSION DISEASE PATIENT ON CHRONIC PARENTERAL NUTRITION

Microvillus inclusion disease (MVID) is a rare form of congenital secretory diarrhea caused by pathogenic MYO5B variants. We present a 2-year-old girl with MVID referred to Nephrology for persistent severe hypophosphatemia. Paradoxically, serum phosphate (PO4) decreased despite graded increases in PO4 supplementation. Her electrolyte profile was otherwise unremarkable aside from mild hypokalemia and hypochloremia. Typical of patients with MYO5B-MVID, nutrition was solely through intravenous supplementation (~0.5L of 0.9% for 6h and ~1.1L of parenteral nutrition (PN) for 12h). Severe hypophosphatemia has been described in other MVID patients on PN: it was hypothesized to be due to proximal tubular dysfunction related to the pathogenic MYO5B genotype because MYO5B is expressed in proximal tubule cells. 

To elucidate the physiology of phosphate wasting and solute handling, the patient underwent a 24-hour metabolic balance study during alternating periods with and without PN and intravenous fluids, with serial paired serum, urine and stool electrolyte measurements. After discharge, serial paired studies were continued for twenty-four months.

A 24h balance study (on/off PN) revealed that tubular reabsorption of phosphate (TRP) was the lowest (49%), and fractional excretion of sodium (FENa) highest (~2%), while on PN. These values improved after 6 hours without PN. Concurrent stool and urine electrolyte analysis confirmed that the negative PO4 balance was exclusively due to renal losses, without other evidence of a proximal tubulopathy. It also confirmed that 100% of chloride losses were from stool, and 85% of potassium losses were from urine. We reasoned that the combination of high PN and IV fluid PO4 and sodium (Na) loads caused an obligate phosphaturic response by upregulating parathormone (PTH: 115 ng/L ref 16-63) and fibroblast growth factor 23 (FGF23: 452 RU/mL ref <230). We first corrected the hypokalemia and hypochloremia (allowing urine chloride to be detectable) while also reducing PN Na by 13% over a 4-week period. This resulted in a moderate improvement in her serum PO4, TRP values and FENa. Then, we reduced PN PO4 by 70% over the next 6 months; by then, serum PO4 and TRP were normal. We also noted other factors that could have influenced the degree of phosphaturia: daily fluctuations in volume status (5-7%) through isotonic saline infusion and elevation in intrarenal dopamine through adjuvant clonidine therapy. She eventually underwent an elective enterotomy to help reduce her diarrheal and electrolyte losses. She remains on chronic PN with normal serum electrolytes.

We propose that excessive PN Na and PO4, hypokalemia, hypochloruria, and elevated intrarenal dopamine contributed to the inappropriate phosphaturic response observed in the context of ongoing severe hypophosphatemia. Clinically, increasing IV phosphate supplementation is usually prescribed reflexively to hypophosphatemic patients. Our case highlights that a counterintuitive reduction in PN Na and PO4 was critical to reducing renal PO4 wasting and normalizing serum levels. It also provides robust evidence against an important role for MYO5B in phosphate handling at the proximal tubule since normal levels were achieved only through judicious, physiology-informed changes to her IV supplementation regimen. A prior version of this abstract was presented at IPNA 2025