ESPN 54th Annual Meeting

ESPN 2022


 
PROXIMAL TUBULOPATHY AND SEVERE MULTI-ORGAN DYSFUNCTION IN AN INFANT WITH NEK-8 MUTATION
ALEJANDRO ZARAUZA SANTOVEÑA 1 LAURA GARCIA ESPINOSA 1 GEMA MUñOZ BARTOLO 2 CéSAR ABELLEIRAS PARDEIRO 3 JULíAN NEVADO BLANCO 4 LAURA ESPINOSA ROMáN 1

1- PEDIATRIC NEPHROLOGY. HOSPITAL UNIVERSITARIO LA PAZ. MADRID.
2- PEDIATRIC HEPATOLOGY. HOSPITAL UNIVERSITARIO LA PAZ. MADRID.
3- PEDIATRIC CARDIOLOGY. HOSPITAL UNIVERSITARIO LA PAZ. MADRID.
4- INGEMM (INSTITUO DE GENéTICA MéDICA Y MOLECULAR ), HULP-IDIPAZ AND CIBERER. MADRID SPAIN
 
Introduction:

 NEK-8 gene encodes a ciliary protein involved in organ development. Mutations in NEK-8 have been described as causing nephronophtisis, although renal phenotype can be diverse. Multiorgan involvement has been reported, such as hepatopathy or cardiomyopathy, usually with poor evolution. 

Material and methods:

 We present a case of a child with severe hepatic dysfunction, cardiac involvement and a rare renal presentation including CAKUT and proximal Fanconi tubulopathy.

Results:

 Male infant born full-term from healthy non-consanguineous parents. Prenatal ultrasound showed severe left hydronephrosis with thickened parenchyma and cysts. Postnatal evaluation confirmed functional annulment of left kidney, with normal right kidney. Cystography showed mild left vesicoureteral reflux. After birth he developed severe and progressive cholestasis with hypoacolia. Etiological study of cholestasis, including exploratory laparoscopy, hepatic biopsy and genetic study, was negative. After finding of hyperchloremic metabolic acidosis, a tubular function study revealed signs of proximal tubulopathy (hyperuricosuria, glycosuria, mild renal phosphate loss, low molecular weight proteinuria, generalized aminoaciduria). Sodium bicarbonate was initiated at 3 months, and common causes of tubulopathy with hepatopathy were ruled out.

Liver disease progressed to cirrhosis and was complicated by an arterio-portal shunt leading to congestive heart failure and requiring embolization. Finally, at 10 months of age he received a liver transplant, without complications and good further liver function. After liver transplantation, he had hypertension and progressive declining in glomerular filtration rate. He currently has stage 3 CKD with an estimated GFR of 33 mL/min/1.73m2. Cardiologically, he maintains complex mitral valve disease with good myocardial function.

At 20 months, a NGS renal disease panel confirmed two non-described missense mutations (compound heterozygosis) in NEK-8, pending parental study.

Conclusions:

 Renal manifestations of NEK8 mutations may include unusual manifestations. Accurate genetic diagnosis provides prognostic information and allows anticipation of potential complications.