Skip to content
How It Works
Explore
Ask a Question Resources Pricing
Who It's For
Patients
Decode results, prep for appointments, weigh options.
Caregivers & advocates
Carry the research load for someone you love.
Providers & clinicians
Resources for patients in your practice.
Log In Sign Up
PubMed This is a summary of 36 peer-reviewed journal articles Updated
Nephrology · Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC): A Patient Guide

At a Glance

FHHNC is an inherited kidney disorder caused by CLDN16 or CLDN19 variants that waste magnesium and calcium, leading to low blood magnesium and kidney calcifications. Care includes individualized fluids, magnesium, monitoring, and sometimes transplantation; CLDN19 can also affect vision.

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC) is a rare, inherited condition that changes how the kidneys process essential minerals. In a healthy body, the kidneys filter blood and carefully reclaim vital minerals like magnesium and calcium back into the bloodstream. For those living with FHHNC, a genetic defect impairs this reabsorption process [1][2]. Instead of being saved, these minerals slip away and are lost in the urine. This leads to chronically low magnesium levels in the blood and a buildup of calcium deposits (nephrocalcinosis) within the kidney tissue itself [3][4].

The roots of this condition lie in pathogenic variants (mutations) of either the CLDN16 or CLDN19 genes. These genes provide instructions for proteins that help seal the kidney’s microscopic filtering tubes. While both genetic variants lead to similar kidney challenges, the CLDN19 variant is unique because its proteins are also used in the retina of the eye. Individuals with the CLDN19 mutation frequently face vision-related symptoms—such as severe nearsightedness or structural changes in the eye—alongside their kidney diagnosis [5][6]. Identifying which specific gene is involved is a critical first step in building a care plan that addresses both kidney and eye health [7].

Living with FHHNC requires lifelong, individualized management. Because the kidneys constantly lose minerals and accumulate calcium deposits, patients often experience intense thirst, frequent urination, and muscle cramps [8][9]. While there is no cure for the underlying genetic defect, daily care focuses on supportive measures directed by a specialist. This typically includes carefully prescribed fluid targets to maintain hydration, oral magnesium supplements (which require careful balancing to avoid gastrointestinal side effects), and sometimes medications to reduce calcium loss [1][10].

FHHNC is a progressive condition that often leads to advanced kidney disease, though the timeline varies widely from person to person. For patients who eventually develop advanced kidney failure, a kidney transplant is a recognized treatment option [2]. Because the mineral-wasting defect is specific to the native kidneys, a transplanted kidney with healthy proteins can correct the mineral loss, though it requires lifelong medication and monitoring [11]. By working closely with a specialized nephrology and ophthalmology team, patients and families can safely manage symptoms, track health trends, and plan for the future [7][12].

In this guide

6 chapters

01

Understanding Your FHHNC Diagnosis: CLDN16 and CLDN19

Learn how FHHNC affects magnesium, calcium, and kidney function, and how CLDN16 and CLDN19 variants influence inheritance, eye checks, and treatment planning.

02

Symptoms and Warning Signs of FHHNC

Learn FHHNC warning signs, including excessive thirst, kidney stones, low-magnesium muscle symptoms, seizures, CLDN19 eye changes, and when to seek urgent care.

03

Diagnostic Tests & Monitoring Your Labs

Learn how FHHNC is diagnosed with blood and urine tests, genetic testing, and ultrasound, plus how PTH, eGFR, magnesium, and calcium guide your monitoring.

04

Standard of Care Treatment and Symptom Management

Learn how FHHNC treatment manages fluid loss, low magnesium, high urine calcium, kidney stones, and CKD, including medication risks and kidney transplant.

05

Looking Ahead: Long-Term Outlook and Bone Health

Learn how FHHNC affects kidney function and bone health over time, including PTH monitoring, CKD-MBD, bone-density testing, dialysis, and transplant planning.

06

Kidney Transplantation and Genetic Counseling

Learn how kidney transplant, genetic counseling, and carrier testing apply to FHHNC, including donor evaluation, family planning, and post-transplant care.

Common questions in this guide

What is FHHNC, and what causes it?
FHHNC is a rare inherited kidney disorder. Variants in the CLDN16 or CLDN19 genes impair the kidneys’ ability to reclaim magnesium and calcium, leading to low blood magnesium and calcium deposits in kidney tissue.
How are CLDN16 and CLDN19 forms of FHHNC different?
Both gene variants can cause kidney mineral loss, but CLDN19 variants can also affect proteins used in the retina. People with CLDN19-related disease may have severe nearsightedness or structural eye changes, so the gene result helps guide eye as well as kidney monitoring.
What symptoms can FHHNC cause?
FHHNC may cause intense thirst, frequent urination, and muscle cramps because the kidneys lose important minerals. CLDN19-related disease may also cause vision problems, including severe nearsightedness or other structural changes in the eyes.
How is FHHNC treated?
There is no cure for the underlying genetic defect, so treatment focuses on supportive care. A specialist may prescribe an individualized fluid plan, oral magnesium supplements, and sometimes medication to reduce calcium loss; magnesium doses may need adjustment if they cause gastrointestinal side effects.
How should fluid intake be managed with FHHNC?
Your nephrology team should set a daily fluid target based on your individual needs. Ask for a sick-day plan and specific instructions for fever, vomiting, diarrhea, or hot weather rather than changing your fluid intake without guidance.
Can FHHNC lead to kidney failure or require a transplant?
FHHNC is progressive and often leads to advanced kidney disease, although the timeline differs from person to person. If advanced kidney failure develops, a kidney transplant is a recognized treatment option; the transplanted kidney can correct the mineral loss, but lifelong medication and monitoring are needed.
Should family members consider genetic counseling for FHHNC?
Because FHHNC is inherited, family members may benefit from speaking with a genetic counselor about whether evaluation or testing is appropriate. A counselor can explain what a CLDN16 or CLDN19 result may mean for relatives and future monitoring.

Get notified when new evidence is published on Primary hypomagnesemia with hypercalciuria and nephrocalcinosis.

We monitor PubMed for new peer-reviewed studies on this topic and email a short summary when something meaningful changes.

References

References (12)
  1. 1

    Familial hypomagnesemia with hypercalciuria and nephrocalcinosis.

    Vall-Palomar M, Madariaga L, Ariceta G

    Pediatric nephrology (Berlin, Germany) 2021; (36(10)):3045-3055 doi:10.1007/s00467-021-04968-2.

    PMID: 33595712
  2. 2

    Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: clinical and molecular characteristics.

    Claverie-Martin F

    Clinical kidney journal 2015; (8(6)):656-64 doi:10.1093/ckj/sfv081.

    PMID: 26613020
  3. 3

    In-Depth Bioinformatic Study of the CLDN16 Gene and Protein: Prediction of Subcellular Localization to Mitochondria.

    Rouka E, Liakopoulos V, Gourgoulianis KI, et al.

    Medicina (Kaunas, Lithuania) 2019; (55(8)) doi:10.3390/medicina55080409.

    PMID: 31357502
  4. 4

    Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization.

    Gong Y, Renigunta V, Zhou Y, et al.

    Molecular biology of the cell 2015; (26(24)):4333-46 doi:10.1091/mbc.E15-06-0422.

    PMID: 26446843
  5. 5

    Heterogeneity is a common ground in familial hypomagnesemia with hypercalciuria and nephrocalcinosis caused by CLDN19 gene mutations.

    Vall-Palomar M, Burballa C, Claverie-Martín F, et al.

    Journal of nephrology 2021; (34(6)):2053-2062 doi:10.1007/s40620-021-01054-6.

    PMID: 33929692
  6. 6

    Claudin 19-based familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a sibling pair.

    Sharma S, Place E, Lord K, et al.

    Clinical nephrology 2016; (85(6)):346-52 doi:10.5414/CN108783.

    PMID: 27007868
  7. 7

    Whole exome sequencing reveals a pathogenic homozygous CLDN16 mutation in a 17-year-old patient with familial hypomagnesemia with hypercalciuria and nephrocalcinosis: A case report.

    Wang F, Adeerjiang Y, Xing HQ, Jiang S

    Medicine 2025; (104(33)):e43839 doi:10.1097/MD.0000000000043839.

    PMID: 40826740
  8. 8

    Hypomagnesemia with Hypercalciuria Leading to Nephrocalcinosis, Amelogenesis Imperfecta, and Short Stature in a Child Carrying a Homozygous Deletion in the CLDN16 Gene.

    Radonsky V, Kizys MML, Dotto RP, et al.

    Calcified tissue international 2020; (107(4)):403-408 doi:10.1007/s00223-020-00726-y.

    PMID: 32710267
  9. 9

    Recurrent Nephrolithiasis and Beyond: The Long Diagnostic Odyssey of a Case of CLDN16 Mutation.

    Bhuiyan AAN, Akter N, Haq T, et al.

    Clinical case reports 2025; (13(12)):e71530 doi:10.1002/ccr3.71530.

    PMID: 41306405
  10. 10

    Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis: A Case Report of Compound Heterozygous Variants in the CLDN16 Gene Inherited From Symptomatic Heterozygous Carriers.

    Ceol M, Sgrò E, Anglani F, et al.

    Case reports in nephrology and dialysis 2026; (16(1)):162-170 doi:10.1159/cnd/abxag006.

    PMID: 42960388
  11. 11

    Kidney Transplantation From a Heterozygous CLDN19 Carrier in a Child With FHHNC: A 2-Year Follow-Up.

    Erdoğan H, Danışoğlu ME, Çelik H, et al.

    Pediatric transplantation 2026; (30(10)):e70495 doi:10.1111/petr.70495.

    PMID: 42855920
  12. 12

    Familial hypomagnesemia with hypercalciuria and nephrocalcinosis treated with living-donor kidney transplantation: case report.

    Kaba A, Kaku K, Shingaki K, et al.

    CEN case reports 2026; (15(3)).

    PMID: 42095997

This page is for informational purposes only and does not constitute medical advice. Your nephrologist, genetic counselor, and ophthalmologist can tailor monitoring and treatment to you or your child.