Atypical presentation of familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a patient with a new claudin-16 gene mutation

Vianna, Júlia Guasti P.; Simor, Thiago Gabriel; Senna, Pamella; Bortoli, M R De; Costalonga, Everlayny Fiorot; Seguro, Antônio Carlos; Luchi, Weverton Machado

doi:10.5414/cncs109595

Cited by 8 publications

(3 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Additionally, vitamin D deficiency per se could induce proteinuria, yet, Pt #2 continued to have proteinuria after vitamin D replacement. Hypercalciuria and even nephrolithiasis has been described in heterozygous family members of index cases with FHHNC [34,35]. The clinical, laboratory, and radiological examinations of the genetically heterozygous parents of both patients were normal in our study.…”

Section: Tablesupporting

confidence: 39%

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features

et al. 2021

View full text Add to dashboard Cite

Biallelic loss of function mutations in the CLDN16 gene cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC), and chronic kidney disease. Here we report two cases of FHHNC with diverse clinical presentations and hypercalcemia in one as a novel finding. Pt#1 initially presented with urinary tract infection and failure to thrive at 5.5 months of age to another center. Bilateral nephrocalcinosis, hypercalcemia (Ca: 12.2 mg/dl), elevated parathyroid hormone (PTH) level, and hypercalciuria were detected. Persistently elevated PTH with high/normal Ca levels led to subtotal-parathyroidectomy at the age of 2.5. However, PTH levels remained elevated with progressive deterioration in renal function. At 9-year-old, she was referred to us for evaluation of hyperparathyroidism and, hypomagnesemia together with hypercalciuria, elevated PTH with normal Ca levels, and medullary nephrocalcinosis were detected. Compound heterozygosity of CLDN16 variants (c.715G>A, p.G239R; and novel c.360C>A, p.C120*) confirmed the diagnosis. Pt#2 was a 10-month-old boy, admitted with irritability and urinary crystals. Hypocalcemia, hypophosphatemia, elevated PTH and ALP, low 25(OH)D levels, and radiographic findings of rickets were detected. However, additional findings of hypercalciuria and bilateral nephrocalcinosis were inconsistent with the nutritional rickets. Low/normal serum Mg levels suggested the diagnosis of FHHNC which was confirmed genetically as a homozygous missense (c.602G > A; p.G201E) variant in CLDN16. Yet, hypocalcemia and hypomagnesemia persisted in spite of treatment. In conclusion, FHHNC may present with diverse clinical features with mild hypomagnesemia leading to secondary hyperparathyroidism with changing Ca levels from low to high. Early and accurate clinical and molecular genetic diagnosis is important for proper management.

show abstract

Section: Tablesupporting

confidence: 39%

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Patients commonly present with recurrent urinary tract infections, hematuria and abacterial leukocyturia, nephrolithiasis, polyuria/polydipsia with nycturia from infanthood [50-52,59-62] due to impaired urinary concentrating ability [54]. Hypocitraturia is frequently mentioned [45,52,54,55,61,[63][64][65][66][67] but urinary acidification capacity has seldom been assessed. A few reports mention distal defect of urinary acidification [45,54,59]: incomplete distal renal tubular acidosis may affect up to 80% of patients [45,66] but it remains unclear whether it is directly caused by CLDN16/19 mutation or by nephrocalcinosis.…”

Section: Phenotypementioning

confidence: 99%

Claudins in Renal Physiology and Pathology

Prot-Bertoye

Houillier

2020

Genes

View full text Add to dashboard Cite

Claudins are integral proteins expressed at the tight junctions of epithelial and endothelial cells. In the mammalian kidney, every tubular segment express a specific set of claudins that give to that segment unique properties regarding permeability and selectivity of the paracellular pathway. So far, 3 claudins (10b, 16 and 19) have been causally traced to rare human syndromes: variants of CLDN10b cause HELIX syndrome and variants of CLDN16 or CLDN19 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis. The review summarizes our current knowledge on the physiology of mammalian tight junctions and paracellular ion transport, as well as on the role of the 3 above-mentioned claudins in health and disease. Claudin 14, although not having been causally linked to any rare renal disease, is also considered, because available evidence suggests that it may interact with claudin 16. Some single-nucleotide polymorphisms of CLDN14 are associated with urinary calcium excretion and/or kidney stones. For each claudin considered, the pattern of expression, the function and the human syndrome caused by pathogenic variants are described.

show abstract

“…Overall, these supportive treatments do not negate the progression of renal dysfunction, and renal replacement therapies are commonly necessitated before adulthood. Renal transplantation is the ideal option: the loss-of-function channelopathy is not present in the renal allograft so renal calcium and magnesium handling are normalised and there is no disease recurrence [31].…”

Section: Cldn16 and Cldn19 Mutationsmentioning

confidence: 99%

Nephrocalcinosis: A Review of Monogenic Causes and Insights They Provide into This Heterogeneous Condition

Dickson

Sayer

2020

IJMS

View full text Add to dashboard Cite

The abnormal deposition of calcium within renal parenchyma, termed nephrocalcinosis, frequently occurs as a result of impaired renal calcium handling. It is closely associated with renal stone formation (nephrolithiasis) as elevated urinary calcium levels (hypercalciuria) are a key common pathological feature underlying these clinical presentations. Although monogenic causes of nephrocalcinosis and nephrolithiasis are rare, they account for a significant disease burden with many patients developing chronic or end-stage renal disease. Identifying underlying genetic mutations in hereditary cases of nephrocalcinosis has provided valuable insights into renal tubulopathies that include hypercalciuria within their varied phenotypes. Genotypes affecting other enzyme pathways, including vitamin D metabolism and hepatic glyoxylate metabolism, are also associated with nephrocalcinosis. As the availability of genetic testing becomes widespread, we cannot be imprecise in our approach to nephrocalcinosis. Monogenic causes of nephrocalcinosis account for a broad range of phenotypes. In cases such as Dent disease, supportive therapies are limited, and early renal replacement therapies are necessitated. In cases such as renal tubular acidosis, a good renal prognosis can be expected providing effective treatment is implemented. It is imperative we adopt a precision-medicine approach to ensure patients and their families receive prompt diagnosis, effective, tailored treatment and accurate prognostic information.

show abstract

Atypical presentation of familial hypomagnesemia with hypercalciuria and nephrocalcinosis in a patient with a new claudin-16 gene mutation

Cited by 8 publications

References 16 publications

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features

Familial Hypomagnesemia with Hypercalciuria and Nephrocalcinosis Due to CLDN16 Gene Mutations: Novel Findings in Two Cases with Diverse Clinical Features

Claudins in Renal Physiology and Pathology

Nephrocalcinosis: A Review of Monogenic Causes and Insights They Provide into This Heterogeneous Condition

Contact Info

Product

Resources

About