X-Linked Hypophosphatemic Rickets: Report of a Novel PHEX Mutation and Cinacalcet as Adjuvant Therapy in the Mineral Metabolism Control

2021 ◽  
Author(s):  
Daniela Cavaco ◽  
Pedro Amaro ◽  
Joana Simões-Pereira ◽  
Maria Conceição Pereira
Keyword(s):  
Mineral Metabolism ◽  
Bone Fragility ◽  
Hypophosphatemic Rickets ◽  
Heterozygous Mutation ◽  
Tertiary Hyperparathyroidism ◽  
Term Administration ◽  
Phex Gene ◽  
Serum Pth

Abstract X-linked hypophosphatemic rickets (XLH) is a rare disease caused by a mutation in the PHEX gene, located on the X chromosome. This gene encodes the phosphate regulating endopeptidase, and its inactivation leads to increased levels of circulating phosphatonins responsible for renal phosphate loss. The treatment of XLH is still carried out with long-term administration of phosphate and calcitriol, which can be complicated by hyperparathyroidism, nephrocalcinosis, renal failure and hypertension. We describe the case of a four-decades follow-up patient with XLH. When she was diagnosed, at 19, due to bone pain and deformities, she was put on therapy with phosphorus and cholecalciferol. Despite the clinical improvement, serum phosphorus remained difficult to control. At the age of 44, she developed tertiary hyperparathyroidism and was submitted to parathyroidectomy. Five years later, parathyroid hyperfunction recurred. This time, cinacalcet was started, 30 mg alternating with 60 mg/day. Currently, she is 59 years-old and remains with controlled mineral metabolism. The genetic study of this patient revealed a nonsense heterozygous mutation (c.501G> A) in PHEX gene that was not previously described. In this case, the off-label use of cinacalcet resulted in the normalization of serum PTH and phosphorus levels, eliminated recurrent secondary hyperparathyroidism, which aggravates the bone fragility inherent to XLH and prevented a new parathyroidectomy. This report also adds important information to the genetic basis of XLH with the identification of a new nonsense mutation of the PHEX gene.

Hereditary hypophosphatemic rickets and craniosynostosis

2021 ◽  
Vol 0 (0) ◽  
Author(s):  
María Alejandra Arenas ◽  
Sebastián Jaimovich ◽  
Natalia Perez Garrido ◽  
Mariana del Pino ◽  
Gisela Viterbo ◽  
...  
Keyword(s):  
Chiari I Malformation ◽  
Hypophosphatemic Rickets ◽  
Clinical Notes ◽  
Long Term Follow Up ◽  
Phex Gene ◽  
Chiari I ◽  
Normal Head

Abstract Background Craniosynostosis is an underdiagnosed complication associated with hypophosphatemic rickets. The study aims to describe the clinical and auxological characteristic of children with hypophosphatemic rickets and craniosynostosis, describe the usual treatment, and compare the characteristics with those of children without craniosynostosis. Methods and patients An observational and retrospective cohort study was conducted. Clinical notes and cranial images were reviewed. Out of 96 children, only the 50 patients who had skull images were included. Results Out of 50 patients, 26 (15 males) had craniosynostosis (52%). No differences were observed in birth size, age, height, body proportions, alkaline phosphatase, serum phosphate, or percent tubular reabsorption of phosphate at first appointment among children with or without craniosynostosis. Among patients with craniosynostosis, dolichocephaly was prevalent. The sagittal suture was affected in all patients with craniosynostosis, with 19 of 26 children (73%) affected with isolated scaphocephaly. Pan-sutural craniosynostosis was present in 7 children (27%). None of the children had microcephaly, 7 of them presented macrocephaly and, in the remaining subjects, head circumference was normal. Five patients had undergone at least 1 cranial remodeling surgery. One patient with craniosynostosis was diagnosed with a Chiari I malformation. Molecular characterization of PHEX gene was performed in 14 cases. Conclusions Craniosynostosis is an underdiagnosed complication of hypophosphatemic rickets. Many patients with normal head size and growth may go undiagnosed, thus it is important to consider this association for early diagnosis and possible surgical treatment. A multidisciplinary approach is necessary for a correct long-term follow-up.

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

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
Yun Ann Chin ◽  
Yi Zhao ◽  
Gerald Tay ◽  
Weiying Sim ◽  
Chun Yuen Chow ◽  
...  
Keyword(s):  
Gene Deletion ◽  
Perioperative Management ◽  
Delayed Diagnosis ◽  
Accurate Diagnosis ◽  
Hypophosphatemic Rickets ◽  
Multidisciplinary Management ◽  
Tertiary Hyperparathyroidism ◽  
Phex Gene ◽  
Prevalent Form

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.

Hypophosphatemic rickets: results of a long-term follow-up

2005 ◽  
Vol 21 (2) ◽  
pp. 230-234 ◽  
Author(s):  
Maria Helena Vaisbich ◽  
Vera H. Koch
Keyword(s):  
Hypophosphatemic Rickets ◽  
Long Term Follow Up

scholarly journals Genotype and Phenotype Analysis in X-Linked Hypophosphatemia

2021 ◽  
Vol 9 ◽  
Author(s):  
Peong Gang Park ◽  
Seon Hee Lim ◽  
HyunKyung Lee ◽  
Yo Han Ahn ◽  
Hae Il Cheong ◽  
...  
Keyword(s):  
Serum Phosphate ◽  
Hypophosphatemic Rickets ◽  
Phosphate Level ◽  
Serum Phosphate Level ◽  
Onset Age ◽  
Presenting Symptoms ◽  
Truncating Mutation ◽  
Mutation Group

Background: X-linked hypophosphatemia (XLH) is the most frequent form of hypophosphatemic rickets and is caused by mutations in the PHEX gene. We analyzed genotype-phenotype correlations in XLH patients with proven PHEX mutations.Methods:PHEX mutations were detected in 55 out of 81 patients who clinically presented with hypophosphatemic rickets. The patients were grouped into nontruncating (n = 9) and truncating (n = 46) mutation groups; their initial presentation as well as long-term clinical findings were evaluated according to these groups.Results: Initial findings, including presenting symptoms, onset age, height standard deviation scores (SDS), and laboratory tests, including serum phosphate level and tubular resorption of phosphate, were not significantly different between the two groups (onset age: nontruncating mutation group, 2.0 years, truncating mutation group, 2.2 years; height SDS: nontruncating mutation group, −1.9, truncating mutation group, −1.7; serum phosphate: nontruncating mutation group, 2.5 mg/dL, truncating mutation group, 2.6 mg/dL). However, at their last follow-up, the serum phosphate level was significantly lower in patients with truncating mutations (nontruncating mutation group: 3.2 mg/dl, truncating mutation group: 2.3 mg/dl; P = 0.006). Additionally, 62.5% of patients with truncating mutations developed nephrocalcinosis at their last follow-up, while none of the patients with nontruncating mutations developed nephrocalcinosis (P = 0.015). Orthopedic surgery due to bony deformations was performed significantly more often in patients with truncating mutations (52.3 vs. 10.0%, P = 0.019).Conclusion: Although considerable inconsistency exists regarding the correlation of truncating mutations and their disease phenotype in several other studies, we cautiously suggest that there would be genotype-phenotype correlation in some aspects of disease manifestation after long-term follow-up. This information can be used when consulting patients with confirmed XLH regarding their disease prognosis.

scholarly journals P1748PARATHYROIDECTOMY REMAINS EFFECTIVE FOR TREATING TERTIARY HYPERPARATHYROIDISM: LONG-TERM RESULTS OF A RANDOMIZED STUDY

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Ana Coloma Lopez ◽  
Pablo Moreno ◽  
Jose-Vicente Torregrosa ◽  
Nuria Montero ◽  
Anna Manonelles ◽  
...  
Keyword(s):  
Kidney Transplant ◽  
Serum Calcium ◽  
Randomized Study ◽  
Fragility Fractures ◽  
Long Term Results ◽  
Subtotal Parathyroidectomy ◽  
Tertiary Hyperparathyroidism ◽  
Increased Risk

Abstract Background and Aims Tertiary hyperparathyroidism is a common cause of hypercalcemia after kidney transplant (KT) and has been associated with renal dysfunction, loss bone mineral density and increased risk of fracture, vascular calcification, and increased risk of cardiovascular events. Long clinical management remains controversial. The aim of this study is to evaluate the long-term effectiveness and safety of parathyroidectomy versus cinacalcet in patients with persistent hyperparathyroidism. Method A 12-month prospective, multicenter, randomized study demonstrated than subtotal parathyroidectomy is more effective than cinacalcet for controlling hypercalcemia. Now, we evaluate in the same cohort of patients if this effect is maintained after 5 years of follow-up. Laboratory assessment included serum calcium, serum phosphate, intact parathyroid hormone (iPTH), calcidiol levels, estimated glomerular filtration rate and proteinuria at 2, 3, 4 and 5 year follow-up. Therapeutic details about the use of vitamin D, calcium supplementation and phosphate binders were compiled. Fragility fractures were also collected. Results In total, 24 patients had data available at 5 years, 13 in the cinacalcet group and 11 in the parathyroidectomy group. At 5 years, six of 13 patients in the cinacalcet group and ten of 11 patients in the parathyroidectomy group (p=0.015) showed normocalcemia (Figure 1). Subtotal parathyroidectomy retained a greater reduction of iPTH compared with cinacalcet group (Figure 2). No differences were observed in kidney function and incidence of fragility fractures between both groups. In relation of treatment, 8 of 13 patients in cinacalcet group maintained treatment with cinacalcet after 5 years follow-up. Conclusion Subtotal parathyroidectomy is more effective in long term to maintain normal serum calcium and iPTH compared with cinacalcet in kidney transplant patients with tertiary hyperparathyroidism.

scholarly journals The Effect of Nasal Steroid Administration on Intraocular Pressure

2007 ◽  
Vol 86 (7) ◽  
pp. 394-395 ◽  
Author(s):  
Christos Spiliotopoulos ◽  
Nicholas S. Mastronikolis ◽  
Ioannis K. Petropoulos ◽  
Ephigenia K. Mela ◽  
Panos D. Goumas ◽  
...  
Keyword(s):  
Intraocular Pressure ◽  
Systemic Steroid ◽  
Long Term Effects ◽  
Steroid Administration ◽  
Nasal Steroids ◽  
Term Administration ◽  
Nasal Steroid ◽  
Iop Elevation

The effect of systemic steroid administration on intraocular pressure (IOP) is well established. However, less attention has been paid to the effect of steroids when administered in a nasal spray. We conducted a study to investigate a possible association between nasal steroids and elevated IOP in 54 patients who were being treated for allergic rhinitis. IOP was measured before the patients started therapy and thereafter every 5 days during that therapy. Follow-up ranged from 27 to 35 days (mean: 31). Statistical analysis revealed no significant elevation in IOP after nasal steroid administration. It seems that short-term administration of nasal steroids does not cause significant IOP elevation. Nevertheless, their long-term effects on this pressure should be investigated.

Improvement of Walking Distance by Defibrotide in Patients with Intermittent Claudication

2000 ◽  
Vol 83 (05) ◽  
pp. 672-677 ◽  
Author(s):  
E. Marubini ◽  
S. Coccheri ◽  
G. G. Nenci ◽  
F. Violi
Keyword(s):  
Intermittent Claudication ◽  
Walking Distance ◽  
Controlled Study ◽  
Double Blind ◽  
Intention To Treat ◽  
Term Administration ◽  
One Year ◽  
Present Trial

SummaryDefibrotide is an antithrombotic drug which enhances prostacyclin production and activates fibrinolytic system. The aim of this study was to investigate the improvement of walking distance in patients with intermittent claudication treated with defibrotide.DICLIS was a double blind, placebo-controlled study which included patients with walking distance autonomy at a standardized treadmill test ≤350 ≥100 meters. A total of 310 patients were randomly allocated to placebo (n = 101), defibrotide 800 mg/day (n = 104) or defibrotide 1200 mg/day (n = 105).During a one year follow-up, the Absolute Walking Distance (AWD) was measured six times (0, 30, 60, 90, 180, 360 days).Similar improvement in walking distance was found in the three groups until the 90th day; thereafter placebo group showed no further increase, while AWD continued to increase in the defibrotide groups. Between the 180th and 360th day visits, AWD was significantly higher (P <0.01) in patients given defibrotide than in patients given placebo. No difference in efficacy was observed between the two dosages of defibrotide. No differences in side effects were observed among the three groups.The results of the present trial suggest that long-term administration of defibrotide improves walking distance in patients with intermittent claudication. Abbreviations: DICLIS = Defibrotide Intermittent CLaudication Italian Study, AWD = Absolute Walking Distance, IC = Intermittent Claudication, PVD = Peripheral Vascular Disease, LVOCF = Last Valid Observation Carried Forward, ITT = Intention-To-TreatAppendix, please see p. 676.

scholarly journals Normocalcemic primary hyperparathyroidism: long-term follow-up associated with multiple adenomas

2014 ◽  
Vol 58 (5) ◽  
pp. 583-586 ◽  
Author(s):  
Larissa Pimentel ◽  
Sirley Portela ◽  
Alyne Loureiro ◽  
Francisco Bandeira
Keyword(s):  
Primary Hyperparathyroidism ◽  
Serum Calcium ◽  
Normal Serum ◽  
T Score ◽  
Sestamibi Scan ◽  
Normal Serum Calcium ◽  
Long Term Follow Up ◽  
Serum Pth

Normocalcemic primary hyperparathyroidism (NPHPT) is a condition characterized by elevation of the parathyroid hormone (PTH) in the presence of normal serum calcium and the absence of secondary causes. The case described illustrates the long-term follow-up of a postmenopausal woman with NPHPT patient who progressed with multiple adenomas. This case reports a 77-year-old female who has chronic generalized pain and osteoporosis. Her initial serum PTH was 105 pg/mL, with total serum calcium of 9.6 mg/dL, albumin 4.79 g/dL, phosphorus 2.8 mg/dL, and 25OHD after supplementation was 34.6 ng/mL. The bone densitometry (BMD) results were as follows: lumbar spine: T-score -3.0, femoral neck: T-score -2.6 and distal radius: -4.2. Other causes of secondary hyperparathyroidism were ruled out and cervical ultrasound and Tc-99-Sestamibi scan were negative. She used oral alendronate and three infusions of zoledronic acid for treatment of osteoporosis. In the 10th year of follow-up, after successive negative cervical imaging, ultrasound showed a nodule suggestive of an enlarged right inferior parathyroid gland. PTH levels in fluid which was obtained during fine-needle aspiration (FNA) were over 5,000 pg/mL and a Sestamibi scan was negative. The patient underwent parathyroidectomy, and a histological examination confirmed parathyroid adenoma. Post-operatively serum PTH remained elevated in the presence of normal serum calcium levels. A follow-up cervical ultrasound showed a new solid nodule suggestive of an enlarged right superior parathyroid gland. PTH levels in the aspiration fluid were remarkably high. A second parathyroidectomy was performed, with the excision of a histologically confirmed parathyroid adenoma. In conclusion, this is an unusual presentation of NPHPT and highlights the long-term complications.

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