1
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Delayed Diagnosis, Difficult Decisions: Novel Gene Deletion Causing X-Linked Hypophosphatemia in a Middle-Aged Man with Achondroplastic Features and Tertiary Hyperparathyroidism

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          X-linked hypophosphatemia (XLH) is the most prevalent form of hereditary hypophosphatemic rickets associated with phosphate wasting. However, its diagnosis is often missed, resulting in patients presenting late in the course of the disease when complications such as tertiary hyperparathyroidism and renal failure have already set in. Phosphate and calcitriol replacement, both of which have undesirable consequences of their own, have historically been the main stay of therapy. We describe the case of a 57-year-old gentleman with tertiary hyperparathyroidism, who was mislabelled as having achondroplasia for many years before we made a diagnosis of XLH in him. His XLH was found to be due to a hereto unreported deletion of entire exon 14 with partial deletions of introns 13 and 14 of the PHEX gene. Perioperative management in him was fraught with surgical and medical difficulties including an operation that was technically complicated due to his multiple anatomical deformities. Our case also highlights the critical importance of timely recognition and accurate diagnosis of XLH, as well as the long-term multidisciplinary management that is needed for this disorder.

          Related collections

          Most cited references 17

          • Record: found
          • Abstract: found
          • Article: not found

          Incidence and prevalence of nutritional and hereditary rickets in southern Denmark.

          To estimate the incidence of nutritional rickets and the incidence and prevalence of hereditary rickets. Population-based retrospective cohort study based on a review of medical records. Patients aged 0-14.9 years referred to or discharged from hospitals in southern Denmark from 1985 to 2005 with a diagnosis of rickets were identified by register search, and their medical records were retrieved. Patients fulfilling the diagnostic criteria of primary rickets were included. We identified 112 patients with nutritional rickets of whom 74% were immigrants. From 1995 to 2005, the average incidence of nutritional rickets in children aged 0-14.9 and 0-2.9 years was 2.9 and 5.8 per 100,000 per year respectively. Among immigrant children born in Denmark, the average incidence was 60 (0-14.9 years) per 100,000 per year. Ethnic Danish children were only diagnosed in early childhood and the average incidence in the age group 0-2.9 years declined from 5.0 to 2.0 per 100,000 per year during 1985-1994 to 1995-2005. Sixteen cases of hereditary rickets were diagnosed during the study period giving an average incidence of 4.3 per 100,000 (0-0.9 years) per year. The prevalence of hypophosphatemic rickets and vitamin D-dependent rickets type 1 was 4.8 and 0.4 per 100,000 (0-14.9 years) respectively. Nutritional rickets is rare in southern Denmark and largely restricted to immigrants, but the incidence among ethnic Danish children was unexpectedly high. Hereditary rickets is the most common cause of rickets in ethnic Danish children, but nutritional rickets is most frequent among all young children.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            FGF23, PHEX, and MEPE regulation of phosphate homeostasis and skeletal mineralization.

             L Quarles (2003)
            There is evidence for a hormone/enzyme/extracellular matrix protein cascade involving fibroblastic growth factor 23 (FGF23), a phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), and a matrix extracellular phosphoglycoprotein (MEPE) that regulates systemic phosphate homeostasis and mineralization. Genetic studies of autosomal dominant hypophosphatemic rickets (ADHR) and X-linked hypophosphatemia (XLH) identified the phosphaturic hormone FGF23 and the membrane metalloprotease PHEX, and investigations of tumor-induced osteomalacia (TIO) discovered the extracellular matrix protein MEPE. Similarities between ADHR, XLH, and TIO suggest a model to explain the common pathogenesis of renal phosphate wasting and defective mineralization in these disorders. In this model, increments in FGF23 and MEPE, respectively, cause renal phosphate wasting and intrinsic mineralization abnormalities. FGF23 elevations in ADHR are due to mutations of FGF23 that block its degradation, in XLH from indirect actions of inactivating mutations of PHEX to modify the expression and/or degradation of FGF23 and MEPE, and in TIO because of increased production of FGF23 and MEPE. Although this model is attractive, several aspects need to be validated. First, the enzymes responsible for metabolizing FGF23 and MEPE need to be established. Second, the physiologically relevant PHEX substrates and the mechanisms whereby PHEX controls FGF23 and MEPE metabolism need to be elucidated. Finally, additional studies are required to establish the molecular mechanisms of FGF23 and MEPE actions on kidney and bone, as well as to confirm the role of these and other potential "phosphatonins," such as frizzled related protein-4, in the pathogenesis of the renal and skeletal phenotypes in XLH and TIO. Unraveling the components of this hormone/enzyme/extracellular matrix pathway will not only lead to a better understanding of phosphate homeostasis and mineralization but may also improve the diagnosis and treatment of hypo- and hyperphosphatemic disorders.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: found
              Is Open Access

              Clinical practice recommendations for the diagnosis and management of X-linked hypophosphataemia

              X-linked hypophosphataemia (XLH) is the most common cause of inherited phosphate wasting and is associated with severe complications such as rickets, lower limb deformities, pain, poor mineralization of the teeth and disproportionate short stature in children as well as hyperparathyroidism, osteomalacia, enthesopathies, osteoarthritis and pseudofractures in adults. The characteristics and severity of XLH vary between patients. Because of its rarity, the diagnosis and specific treatment of XLH are frequently delayed, which has a detrimental effect on patient outcomes. In this Evidence-Based Guideline, we recommend that the diagnosis of XLH is based on signs of rickets and/or osteomalacia in association with hypophosphataemia and renal phosphate wasting in the absence of vitamin D or calcium deficiency. Whenever possible, the diagnosis should be confirmed by molecular genetic analysis or measurement of levels of fibroblast growth factor 23 (FGF23) before treatment. Owing to the multisystemic nature of the disease, patients should be seen regularly by multidisciplinary teams organized by a metabolic bone disease expert. In this article, we summarize the current evidence and provide recommendations on features of the disease, including new treatment modalities, to improve knowledge and provide guidance for diagnosis and multidisciplinary care.
                Bookmark

                Author and article information

                Contributors
                Journal
                Case Rep Endocrinol
                Case Rep Endocrinol
                CRIE
                Case Reports in Endocrinology
                Hindawi
                2090-6501
                2090-651X
                2021
                15 April 2021
                : 2021
                Affiliations
                1Department of Endocrinology, Singapore General Hospital, Singapore
                2Department of Clinical Translational Research, Singapore General Hospital, Singapore
                3Department of Head and Neck Surgery, Division of Surgery and Surgical Oncology, Singapore General Hospital, Singapore
                4Department of Pathology, Singapore General Hospital, Singapore
                5Complicated Metabolic Bone Disorders Clinic, Osteoporosis and Bone Metabolism Unit, Department of Endocrinology, Singapore General Hospital, Singapore
                Author notes

                Academic Editor: Micha�l R. Laurent

                Article
                10.1155/2021/9944552
                8064789
                Copyright © 2021 Yun Ann Chin et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                Case Report

                Comments

                Comment on this article