Hypomagnesemia as First Clinical Manifestation of ADTKD-HNF1B: A Case Series and Literature Review.
BACKGROUND
Autosomal dominant tubulointerstitial kidney disease subtype HNF1B (ADTKD-HNF1B) is caused by a mutation in hepatocyte nuclear factor 1 homeobox beta (HNF1B). Although 50-60% of ADTKD-HNF1B patients develop hypomagnesemia, HNF1B mutations are mainly identified in patients with structural kidney defects or diabetes.


METHODS
The current case series describes 3 patients in whom hypomagnesemia proved to be the first clinical manifestation of ADTKD-HNF1B. All patients presented with hypomagnesemia with a high fractional excretion of Mg2+ and hypocalciuria. Exome sequencing performed for analysis of known and candidate hypomagnesaemia genes and subsequent multiplex ligation-dependent probe amplification analysis revealed a large deletion at the chromosome 17q12. Follow-up analysis showed increased blood glucose concentrations in all 3 patients and high hemoglobin A1c levels in 2 out of 3 patients, indicating diabetes mellitus. Although all patients suffered from mild renal insufficiency, only 1 of the 3 patients was shown to have renal cysts on CT.


CONCLUSIONS
The prevalence of HNF1B mutations and the relative contribution of hypomagnesemia to its symptoms are underestimated. Therefore, patients with primary renal magnesium wasting should be tested for HNF1B mutations to ensure early detection and optimal management of ADTKD-HNF1B.
Cas I
CI
van der Made
Ewout J
EJ
Hoorn
Renaud
R
de la Faille
Huseyin
H
Karaaslan
Nine V A M
NV
Knoers
Joost G J
JG
Hoenderop
Rosa
R
Vargas Poussou
Jeroen H F
JH
de Baaij
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002493:Central Nervous System Diseases / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D003743:Dental Enamel / Q000002:abnormalities*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D059472:Exome; D005820:Genetic Testing; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics*; D006801:Humans; D052177:Kidney Diseases, Cystic / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009395:Nephritis, Interstitial / Q000150:complications* / Q000175:diagnosis / Q000235:genetics; D051437:Renal Insufficiency / Q000209:etiology; D015499:Renal Tubular Transport, Inborn Errors / Q000209:etiology*
D001786:Blood Glucose; C496495:HNF1B protein, human; D051539:Hepatocyte Nuclear Factor 1-beta