1 - Pediatric Department, Hospital de Vila Franca de Xira, Portugal
2 - Children and Adolescents Department, Centro Hospitalar Lisboa Central, Portugal.
3 - Nephrology Unit; Women, Children and Adolescents Department, Centro Hospitalar Lisboa Central, Portugal
4 - NICU, Maternidade Dr. Alfredo da Costa. Women, Children and Adolescents Department, Centro Hospitalar Lisboa Central, Portugal
5 - Medical Genetics Department, Centro Hospitalar Lisboa Central, Portugal
- 8th Congress of the International Pediatric Nephrology Association, Venice (Italy), October 2019 (Poster).
- Abstract published in: Pediatr Nephrol (2019) 34:2043
Introduction: Urinary ion excretion-absorption disturbances may be observed in addition tomultisystemic symptoms and could be the diagnostic key in several diseases. The receptor of epidermal growth factor (EGFR) affects apical urine magnesium reabsorption besides its dermatological known function.
Case report: Two females, both born to consanguineous Portuguese Roma parents, were admitted to the Neonatal Intensive Care Unit due to prematurity and low birth weight. They were born at 30th and 33rd weeks of gestation by an emergency caesarean delivery due of fetal distress. Case 1 had prenatal diagnosis of severe polyhydramnios, increased bladder volume and nephromegaly. At birth they presented with immature, erythematous and friable skin and global alopecia. Their weight loss was 22% and 23.5%. They also had recurrent Staphylococcus aureus sepsis. From the first days of life, they presented hydroelectrolitic imbalances: polyuria (maximum urine output of 7.5 and 9.9ml/kg/h); hypernatremic dehydration (96mmol/L and 167mmol/L); hypokalemia (2.8mmol/L and 2.2mmol/L) and hypomagnesemia (0.85mg/dl and 1.06mg/dl. Patient 1 also showed ypophosphatemia (3.9 mmol/L) and none had metabolic acidosis or alkalosis. The urine analysis revealed urinary losses of potassium and magnesium with elevated fraccional excretion (FE) of both ions in the two patients (FEK 37% and >35%; FEMg 44% and >23.2%), hypercalciuria (calcium/creatinine 2mg/mg and 3.38mg/mg) and normal urinary chloride excretion. Case 1 also had nephrotic range proteinuria (protein/creatinine 8.9mg/mg). Clinical exome sequencing identified EGFR loss of function mutation in both cases. Both patients died due to infectious and hidroelectrolytic complications.
Conclusion: EGFR, present in basolateral surface of distal convoluted tubule, stimulates apical transcellular magnesium reabsorption through TRPM6 channel. Hypomagnesemia causes increased potassium renal loss, worsening hypokalemia, by disinhibition of ROMK channel and Na+K+-ATPase dysfuntion. EGFR mutation also leads to skin fragility, with recurrent infections, dehydration and hydroelectrolitic imbalances. There are only a few similar cases reported, all with poor prognosis.
Keywords: hypokalemia, hypomagnesemia, tubulopathy