FHHNC
MCID: FML327
MIFTS: 18

Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis (FHHNC)

Categories: Eye diseases, Genetic diseases, Metabolic diseases, Nephrological diseases, Rare diseases

Aliases & Classifications for Familial Primary Hypomagnesemia with Hypercalciuria and...

MalaCards integrated aliases for Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis:

Name: Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis 53 59
Michellis-Castrillo Syndrome 53 59
Fhhnc 53 59

Characteristics:

Orphanet epidemiological data:

59
familial primary hypomagnesemia with hypercalciuria and nephrocalcinosis
Inheritance: Autosomal recessive; Age of onset: Childhood,Infancy; Age of death: adult;

Classifications:



External Ids:

ICD10 via Orphanet 34 E83.4
Orphanet 59 ORPHA306516

Summaries for Familial Primary Hypomagnesemia with Hypercalciuria and...

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 306516DefinitionFamilial primary hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a form of familial primary hypomagnesemia (FPH, see this term), characterized by renal magnesium (Mg) and calcium (Ca) wasting, nephrocalcinosis, kidney failure and, in some cases, severe ocular impairment. Two subtypes of FHHNC are described: FHHNC with severe ocular involvement (FHHNCOI) and without severe ocular involvement (FHHN) (see these terms).EpidemiologyTo date, approximately 200 cases have been reported in the literature.Clinical descriptionThe median age of onset ranges from 1 to 8 years. The most common presenting features are recurrent urinary tract infections, nephrolithiasis, nephrocalcinosis, polyuria, polydipsia, enuresis, hematuria and pyuria. Additional manifestations include failure to thrive, seizures, abdominal pain, muscular tetany and, rarely, rickets. Patients develop chronic kidney disease (CKD) that progresses to end-stage renal disease (ESRD). Two subtypes of FHHNC have been described: FHHNCOI and FHHN. Both forms share identical renal manifestations. By contrast, severe ocular involvement (macular coloboma, pigmentary retinitis, nystagmus, or visual loss) has been described in FHHNCOI, while mild nonspecific ocular involvement (myopia, astigmatism, hypermetropia, or strabismus) has been reported in some cases of FHHN.EtiologyThe disease is caused by mutations in the genes CLDN16 (3q28) and CLDN19 (1p34.2), encoding claudin-16 and claudin-19 respectively. Both proteins are expressed in the thick ascending limb of Henle's loop where they interact to form heteromultimers and play a role in the paracellular reabsorption of Mg and Ca. Inactivating mutations in either gene results in urinary loss of Mg and Ca. Ocular involvement occurs in patients with the CLDN19 mutation as claudin-19 is expressed in retinal pigment epithelium.Diagnostic methodsDiagnosis is based on the triad of hypomagnesemia, hypercalciuria and nephrocalcinosis. Hypocalcemia, hyperuricemia, incomplete distal renal tubular acidosis and hypocitraturia are supportive findings. Parathyroid hormone levels are high before onset of CKD. High fractional urinary excretion of Mg is found while serum level is inappropriately low. Ocular abnormalities are detected by fundoscopy and optical coherence tomography (OCT). Diagnosis is confirmed by genetic screening of CLDN16 and CLDN19.Differential diagnosisDifferential diagnosis includes Bartter syndrome, autosomal dominant hypocalcemia, Dent disease, hereditary hypophosphatemic rickets with hypercalciuria, distal renal tubular acidosis and other tubular disorders causing early nephrocalcinosis (like primary hyperoxaluria) (see these terms).Genetic counselingTransmission is autosomal recessive. Genetic counseling should be offered to at-risk couples (both individuals are carriers of a disease-causing mutation) informing them of the 25% chance of having an affected child.Management and treatmentManagement is mainly supportive and includes administration of Mg supplements in high doses and thiazide diuretics to reduce urinary Ca excretion and the progression of nephrocalcinosis. Indomethacin may be used to increase Ca reabsorption. Therapies aimed at delaying progression of CKD should be provided as well as conventional management strategies for kidney stones. Renal transplantation is the optimal treatment for ESRD. Lens implantation can be proposed to patients suffering from severe ocular abnormalities.PrognosisProgression to ESRD is frequent (50% of patients at 20 years). Follow-up data in one of the described cohorts suggested that patients harboring CLDN19 mutations have a higher risk of progression to CKD than patients with CLDN16 mutations.Visit the Orphanet disease page for more resources.

MalaCards based summary : Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis, also known as michellis-castrillo syndrome, is related to hypomagnesemia 3, renal and hypomagnesemia 5, renal, with or without ocular involvement. Affiliated tissues include kidney.

Related Diseases for Familial Primary Hypomagnesemia with Hypercalciuria and...

Diseases related to Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 17)
# Related Disease Score Top Affiliating Genes
1 hypomagnesemia 3, renal 11.9
2 hypomagnesemia 5, renal, with or without ocular involvement 11.7
3 nephrocalcinosis 10.6
4 end stage renal failure 10.4
5 hypercalciuria, absorptive, 2 10.3
6 autosomal recessive disease 10.3
7 nephrolithiasis, calcium oxalate 10.2
8 kidney disease 10.2
9 branchiootic syndrome 1 10.1
10 myopia 10.1
11 renal osteodystrophy 10.1
12 hyperparathyroidism 10.1
13 renal tubular acidosis 10.1
14 hyperuricemia 10.1
15 chronic kidney disease 10.1
16 distal renal tubular acidosis 10.1
17 slipped capital femoral epiphysis 10.1

Graphical network of the top 20 diseases related to Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis:



Diseases related to Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Symptoms & Phenotypes for Familial Primary Hypomagnesemia with Hypercalciuria and...

Drugs & Therapeutics for Familial Primary Hypomagnesemia with Hypercalciuria and...

Search Clinical Trials , NIH Clinical Center for Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis

Genetic Tests for Familial Primary Hypomagnesemia with Hypercalciuria and...

Anatomical Context for Familial Primary Hypomagnesemia with Hypercalciuria and...

MalaCards organs/tissues related to Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis:

41
Kidney

Publications for Familial Primary Hypomagnesemia with Hypercalciuria and...

Articles related to Familial Primary Hypomagnesemia with Hypercalciuria and Nephrocalcinosis:

(show top 50) (show all 65)
# Title Authors PMID Year
1
A novel CLDN16 mutation in familial hypomagnesemia with hypercalciuria and nephrocalcinosis
. 38
31232269 2019
2
In-Depth Bioinformatic Study of the CLDN16 Gene and Protein: Prediction of Subcellular Localization to Mitochondria. 38
31357502 2019
3
Atypical presentation of familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a patient with a new claudin-16 gene mutation. 38
31119091 2019
4
Familial Hypomagnesemia, Hypercalciuria and Nephrocalcinosis with Novel Mutation. 38
30814796 2019
5
Establishment of urinary exosome-like vesicles isolation protocol for FHHNC patients and evaluation of different exosomal RNA extraction methods. 38
30305086 2018
6
Familial hypomagnesaemia, Hypercalciuria and Nephrocalcinosis associated with a novel mutation of the highly conserved leucine residue 116 of Claudin 16 in a Chinese patient with a delayed diagnosis: a case report. 38
30005619 2018
7
Claudins and nephrolithiasis. 38
29782346 2018
8
A novel homozygous W99G mutation in CLDN-16 gene causing familial hypomagnesemic hypercalciuric nephrocalcinosis in Turkish siblings. 38
30102483 2018
9
Claudin Loss-of-Function Disrupts Tight Junctions and Impairs Amelogenesis. 38
28596736 2017
10
Amelogenesis imperfecta in familial hypomagnesaemia and hypercalciuria with nephrocalcinosis caused by CLDN19 gene mutations. 38
27530400 2017
11
Utility of optical coherence tomography in a case of bilateral congenital macular coloboma. 38
27853022 2016
12
Claudin 19-based familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a sibling pair. 38
27007868 2016
13
A novel mutation in CLDN16 results in rare familial hypomagnesaemia with hypercalciuria and nephrocalcinosis in a Chinese family. 38
27067446 2016
14
Claudin-16 Deficiency Impairs Tight Junction Function in Ameloblasts, Leading to Abnormal Enamel Formation. 38
26426912 2016
15
Biochemical and biophysical analyses of tight junction permeability made of claudin-16 and claudin-19 dimerization. 38
26446843 2015
16
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: clinical and molecular characteristics. 38
26613020 2015
17
Haplotype analysis of CLDN19 single nucleotide polymorphisms in Spanish patients with familial hypomagnesemia with hypercalciuria and nephrocalcinosis. 38
25410674 2015
18
Identification of the first large deletion in the CLDN16 gene in a patient with FHHNC and late-onset of chronic kidney disease: case report. 38
26136118 2015
19
Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis. 38
25720051 2015
20
First report of a novel missense CLDN19 mutations causing familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a Chinese family. 38
25555744 2015
21
Retrospective cohort study of familial hypomagnesaemia with hypercalciuria and nephrocalcinosis due to CLDN16 mutations. 38
25477417 2015
22
[Genetic approach to nephrolithiasis]. 38
26479054 2015
23
Bilateral slipped capital femoral epiphysis in a male adolescent with familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), chronic renal failure, and severe hyperparathyroidism. 38
23455761 2013
24
Hereditary causes of kidney stones and chronic kidney disease. 38
23334384 2013
25
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC): report of three cases with a novel mutation in CLDN19 gene. 38
23538362 2013
26
Impaired paracellular ion transport in the loop of Henle causes familial hypomagnesemia with hypercalciuria and nephrocalcinosis. 38
22731731 2012
27
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis in three siblings having the same genetic lesion but different clinical presentations. 38
21633858 2012
28
Hypomagnesemia-hypercalciuria-nephrocalcinosis and ocular findings: a new claudin-19 mutation. 38
22734304 2012
29
Clinical and molecular characterization of Turkish patients with familial hypomagnesaemia: novel mutations in TRPM6 and CLDN16 genes. 38
21669885 2012
30
Three different causes of hypercalciuria. 38
21698557 2011
31
The role of tight junctions in paracellular ion transport in the renal tubule: lessons learned from a rare inherited tubular disorder. 38
21186073 2011
32
Renal, ocular, and neuromuscular involvements in patients with CLDN19 mutations. 38
21030577 2011
33
A novel mutation of the claudin 16 gene in familial hypomagnesemia with hypercalciuria and nephrocalcinosis mimicking rickets. 38
21848011 2011
34
Mutation in the tight-junction gene claudin 19 (CLDN19) and familial hypomagnesemia, hypercalciuria, nephrocalcinosis (FHHNC) and severe ocular disease. 38
21791920 2011
35
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis: the first four patients in Serbia. 38
20607983 2010
36
Targeted deletion of murine Cldn16 identifies extra- and intrarenal compensatory mechanisms of Ca2+ and Mg2+ wasting. 38
20147368 2010
37
Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium. 38
19706394 2009
38
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: unusual clinical associations and novel claudin16 mutation in an Egyptian family. 38
19165416 2009
39
Insights into driving forces and paracellular permeability from claudin-16 knockdown mouse. 38
19538300 2009
40
Function and regulation of claudins in the thick ascending limb of Henle. 38
18795318 2009
41
Salt and acid-base metabolism in claudin-16 knockdown mice: impact for the pathophysiology of FHHNC patients. 38
18784260 2008
42
Familial hypomagnesaemia with hypercalciuria and nephrocalcinosis (FHHNC): compound heterozygous mutation in the claudin 16 (CLDN16) gene. 38
18816383 2008
43
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis: report of three Turkish siblings. 38
18253757 2008
44
Familial hypomagnesemia with hypercalciuria and nephrocalcinosis in 2 sisters. 38
18327378 2008
45
Claudin-16 and claudin-19 interact and form a cation-selective tight junction complex. 38
18188451 2008
46
Report of a family with two different hereditary diseases leading to early nephrocalcinosis. 38
17899212 2008
47
Transgenic RNAi depletion of claudin-16 and the renal handling of magnesium. 38
17442678 2007
48
A novel PCLN-1 gene mutation in familial hypomagnesemia with hypercalciuria and atypical phenotype. 38
17123117 2007
49
Hypomagnesemia and nephrocalcinosis in a patient with two heterozygous mutations in the CLDN16 gene. 38
17347984 2007
50
Two cases of familial hypomagnesemia with hypercalciuria and nephrocalcinosis: dental findings. 38
17078738 2006

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