{
  "abstract": "Introduction: Familial hypomagnesemia with hypercalciuria and nephrocalcinosis (FHHNC) is a rare autosomal recessive disorder characterized by renal magnesium wasting, hypercalciuria, and early onset of nephrocalcinosis, complicated by progressive chronic renal failure in childhood or adolescence. The disorder is caused by CLDN16 or CLDN19 genes’ pathogenic variants.\n\nCase Presentation: We describe a 22-year-old female patient with a clinical diagnosis of FHHNC in infancy. Detailed clinical evaluation revealed a complex phenotype with early nephrocalcinosis, recurrent self-resolving renal colic episodes, persistent hypomagnesemia, and secondary hyperparathyroidism (HPP). High oral doses of magnesium were required to treat the FHHNC, causing significant gastrointestinal side effects, particularly diarrhea, leading to further magnesium losses. Upon transfer to our adult nephrology unit, the proband’s blood was subjected to genetic analysis using next-generation sequencing with multigene panel testing.\n\nResults: Genetic analysis of the proband revealed compound heterozygous variants in the CLDN16 gene: a novel splice-site variant NC_000003.12 (NM_006580.4):c.382+1G>C in the canonical donor splice consensus sequence, classified as likely pathogenic inherited from the mother with HPP phenotype; a rare missense variant NM_006580.4:c.500G>C p.(Trp167Ser) inherited from the father with hypercalciuria. Due to poor tolerability of conventional oral magnesium salts, she was switched to a Sucrosomial magnesium formulation, which significantly improved her gastrointestinal tolerance and adherence.\n\nConclusion: The novel splice-site variant c.382+1G>C and the previously unreported missense variant p.(Trp167Ser) in CLDN16 expand the mutational spectrum associated with FHHNC. Regarding the mother’s phenotype, a symptomatic carrier of a recessive autosomal disease, our finding suggests the importance of genotype-phenotype analysis in identifying mild forms of FHHNC.",
  "abstract_shown": true,
  "affiliations": [
    "Nephrology Unit, Department of Medicine-DIMED, University of Padua, Padua, Italy",
    "Clinical Genetics Unit, Department of Women and Children’s Health, University of Padua, Padua, Italy"
  ],
  "article_type": "case report",
  "arxiv": null,
  "author_total": 9,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Monica Ceol"
    },
    {
      "affs": [
        0
      ],
      "name": "Elena Sgrò"
    },
    {
      "affs": [
        0
      ],
      "name": "Franca Anglani"
    },
    {
      "affs": [
        0
      ],
      "name": "Giovanna Priante"
    },
    {
      "affs": [
        0
      ],
      "name": "Lucia Federica Stefanelli"
    },
    {
      "affs": [
        0
      ],
      "name": "Martina Cacciapuoti"
    },
    {
      "affs": [
        1
      ],
      "name": "Leonardo Salviati"
    },
    {
      "affs": [
        0
      ],
      "name": "Federico Nalesso",
      "orcid": "0000-0002-1167-2764"
    },
    {
      "affs": [
        0
      ],
      "name": "Dorella Del Prete",
      "orcid": "0000-0003-2141-3472"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/37vcfa5k83cep.bib",
  "cited_by": 0,
  "doi": "10.1159/cnd/abxag006",
  "fulltext_url": "https://pmc.ncbi.nlm.nih.gov/articles/PMC13719199/",
  "id": "37vcfa5k83cep",
  "issns": [
    "2296-9705"
  ],
  "landing_url": "https://doi.org/10.1159/cnd/abxag006",
  "language": "en",
  "licence": "CC-BY-4.0",
  "licence_label": "CC BY 4.0",
  "licence_source": "article",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "heading",
      "Single Case"
    ],
    [
      "openalex",
      "2916|Magnesium in Health and Disease"
    ]
  ],
  "openalex": "W7220901197",
  "pdf_url": "https://karger.com/cnd/article-pdf/doi/10.1159/cnd/abxag006/4591900/000554578.pdf",
  "pmcid": "PMC13719199",
  "pmid": "42960388",
  "published": "2026-10-07",
  "publisher": "Karger Publishers",
  "ris": "https://research.draconitic.com/paper/37vcfa5k83cep.ris",
  "sources": [
    {
      "first_seen": "2026-11-02T12:23:04Z",
      "native_id": "PMC13719199",
      "source": "pmc",
      "url": "https://doi.org/10.1159/cnd/abxag006"
    }
  ],
  "subjects": [
    {
      "field": "medicine",
      "origin": "journal-openalex:F27",
      "subfield": "general"
    }
  ],
  "title": "Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis: A Case Report of Compound Heterozygous Variants in the CLDN16 Gene Inherited From Symptomatic Heterozygous Carriers",
  "title_text": "Familial Hypomagnesemia With Hypercalciuria and Nephrocalcinosis: A Case Report of Compound Heterozygous Variants in the CLDN16 Gene Inherited From Symptomatic Heterozygous Carriers",
  "type": "peer-reviewed",
  "updated_at": "2026-11-02T12:23:04Z",
  "url": "https://research.draconitic.com/paper/37vcfa5k83cep",
  "venue": "Case Reports in Nephrology and Dialysis",
  "versions": []
}