Dataset Information

The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey.

ABSTRACT: Context:X-linked hypophosphatemia (XLH) is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal abnormalities, and growth impairment. We aimed to understand the burden of disease of XLH across the lifespan. Methods:Responses were collected from adults with XLH and parents/caregivers of a child with XLH in an online survey, including multiple-choice and open-ended questions on demographics, disease manifestations, treatment history, assistive device use, and age-specific patient-reported outcomes (PROs). Results:Data were collected from 232 adults with XLH (mean age, 45.6 years; 76% female) and 90 parents/caregivers of a child with XLH (mean age, 9.1 years; 56% female). Mean age recalled for symptom onset was 3.2 years for adults and 1.3 years for children. When surveyed, nearly all children (99%) and 64% of adults were receiving oral phosphate, active vitamin D, or both. Prior participation in a trial investigating burosumab, a fully human monoclonal antibody against FGF23, was reported in 3% of children and 10% of adults; of these respondents, only one child reported current treatment with burosumab at the time of the survey. Both children and adults reported typical features of XLH, including abnormal gait (84% and 86%, respectively), bowing of the tibia/fibula (72% and 77%), and short stature (80% and 86%). Nearly all adults (97%) and children (80%) reported bone or joint pain/stiffness. Adults reported a history of fractures (n/N = 102/232; 44%), with a mean (SD) age at first fracture of 26 (16) years. Adults reported osteophytes (46%), enthesopathy (27%), and spinal stenosis (19%). Mean scores for PROs evaluating pain, stiffness, and physical function were worse than population norms. Analgesics were taken at least once a week by 67% of adults. Conclusions:Despite the common use of oral phosphate and active vitamin D established in the 1980s, children with XLH demonstrate a substantial disease burden, including pain and impaired physical functioning that persists, as demonstrated by similar responses reported in adults with XLH.

SUBMITTER: Skrinar A

PROVIDER: S-EPMC6595532 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey.

Skrinar Alison A Dvorak-Ewell Melita M Evins Ayla A Macica Carolyn C Linglart Agnès A Imel Erik A EA Theodore-Oklota Christina C San Martin Javier J

Journal of the Endocrine Society 20190507 7

<h4>Context</h4>X-linked hypophosphatemia (XLH) is characterized by excess fibroblast growth factor 23 (FGF23), hypophosphatemia, skeletal abnormalities, and growth impairment. We aimed to understand the burden of disease of XLH across the lifespan.<h4>Methods</h4>Responses were collected from adults with XLH and parents/caregivers of a child with XLH in an online survey, including multiple-choice and open-ended questions on demographics, disease manifestations, treatment history, assistive devi ...[more]

PMID: 31259293

Similar Datasets

Project description:X-linked hypophosphatemia (XLH) is the most common hereditary form of rickets and deficiency of renal tubular phosphate transport in humans. XLH is caused by the inactivation of mutations within the phosphate-regulating endopeptidase homolog X-linked (PHEX) gene and follows an X-dominant transmission. It has an estimated frequency of 1 case per 20,000, and over 300 distinct pathogenic variations have been reported that result in an excess of fibroblast growth factor 23 (FGF23) in the serum. Increased levels of FGF23 lead to renal phosphate loss, decreased serum 1,25-dihydroxyvitamin D, and increased metabolism of 1,25-dihydoxyvitamin D, resulting in hypophosphatemia. Major clinical manifestations include rickets, bone deformities, and growth retardation that develop during childhood, and osteomalacia-related fractures or pseudo-fractures, degenerative osteoarthritis, enthesopathy, dental anomalies, and hearing loss during adulthood, which can affect quality of life. In addition, fatigue is also a common symptom in patients with XLH, who experience decreased motion, muscle weakness, and pain, contributing to altered quality of life. The clinical and biomedical characteristics of XLH are extensively defined in bone tissue since skeletal deformations and mineralization defects are the most evident effects of high FGF23 and low serum phosphate levels. However, despite the muscular symptoms that XLH causes, very few reports are available on the effects of FGF23 and phosphate in muscle tissue. Given the close relationship between bones and skeletal muscles, studying the effects of FGF23 and phosphate on muscle could provide additional opportunities to understand the interactions between these two important compartments of the body. By describing the current literature on XLH and skeletal muscle dysfunctions, the purpose of this review is to highlight future areas of research that could contribute to a better understanding of XLH muscular disability and its management.

Project description:Male factor infertility affects about 7% of men in the general population and it can be related to a number of different etiologic factors, including genetic anomalies. Both sex chromosomes are enriched in genes prevalently or exclusively expressed in the testis. Nevertheless only the Y chromosome-linked Copy Number Variants (CNVs) and Y-linked genes have been demonstrated as important contributors to impaired sperm production in humans Data on the potential role of X-linked gene products in spermatogenesis derives mainly from model organisms. X-linked genes seem to be expressed both in pre-meiotic and post-meiotic germ cells in the mouse testis and interestingly those expressed in the post-meiotic cells belong to multicopy gene families. The apparent paucity of X-linked factors in male infertility is most likely related to the scarcity of studies, which focused only on a total of seven genes. No pathogenic mutations causing infertility have, thus far, been described in these genes, with the exception of AR gene In order to advance in the understanding of the role of X-linked CNVs and genes in male infertility, we applied an innovative approach based on high resolution X chromosome specific CGH array. Given that such a detailed analysis of the X chromosome has not been published so far and the testicular function of subjects included in the Genomic Variant Database is unknown (except for 24 X-linked CNVs reported in the recent paper by Tuttelmann), our is the first study providing a detailed analysis of X-linked losses and gains in several hundreds of subjects with known sperm parameters. The study was approved by the local Ethical Committees of the University Hospital Careggi (Italy) and the Fundacio Puigvert (Spain). All participants signed an informed consent. 96 infertile subjects with different grade of spermatogenic impairment (74 azoospermic, 6 mild oligozoospermia and 16 severe oligozoospermic men) and 103 normozoospermic men have been analyzed with aCGH. All known causes of impaired spermatogenesis have been excluded in the patients and testis histology was available for 47 men. The ethnic composition was similar in the controls and patients groups (40% Spanish and 60% Italians). A customized array-CGH platform (custom 8 x 60K, Agilent Technologies) was generated using the eArray software (http://earray.chem.agilent.com/); probes, selected from those available in the Agilent database, covered the whole X chromosome, including Xp and Xq pseudoregions, with an average resolution of 4 Kb. As a reference DNA, we used the same normozoospermic subject for the entire study population. This control DNA was already characterized for CNV content in previous array-CGH experiments against different (8) normospermic controls. In the second part of the study, we performed a case-control study on 31 selected CNVs which appeared to be specific for infertile men after the aCGH analysis. For these selected losses a total of 359 patients and 370 normozoospermic controls were studied. With regard to the gains, 270 patients and 325 controls were analyzed (further phenotypic data are provided in supplementary tables 1a-e). Deletions were analyzed by PCR plus/minus, whereas loss 31 and all the gains have been analyzed with Real Time PCR using TaqMan Copy Number Assay. CNV code Loss or Gain Region Size (kb) Start End 1a GAIN Xp22.33 224,83 1544 226372 4.A GAIN Xp22.33 237,08 153373 390452 5 GAIN Xp22.33 160,10 302644 462740 5.A GAIN Xp22.33 241,98 674222 916206 5.B LOSS Xp22.33 12,63 701071 713696 5.C GAIN Xp22.33 420,72 747358 1168080 11 GAIN Xp22.33 39,73 1347599 1387328 12 GAIN Xp22.33 17,30 1693897 1711194 12.A GAIN Xp22.33 6,61 1693897 1700511 12.B GAIN Xp22.33 683,74 1716023 2399766 14 GAIN Xp22.33 1,40 1896197 1897608 15 LOSS Xp22.33 1,40 1896197 1897608 15.A GAIN Xp22.33 27,94 2382699 2410643 15.B GAIN Xp22.33/22.32 280,09 4206493 4486580 16 LOSS Xp22.32 7,76 4250413 4258174 16.A GAIN Xp22.31 1609,42 6487238 8096662 17 LOSS Xp22.31 31,70 6594834 6626533 18 LOSS Xp22.31 82,00 6756310 6838310 19 GAIN Xp22.31 245,03 7002649 7247676 19.A GAIN Xp22.31 129,96 7961788 8091751 19.B GAIN Xp22.31 177,54 8411159 8588699 20 GAIN Xp22.2 602,10 11104518 11706614 20.A GAIN Xp22.2 665,88 14590604 15256487 20.B GAIN Xp22.13 13,34 18018894 18032238 22 LOSS Xp22.11 24,35 22969648 22993997 23 LOSS Xp21.3 6,69 25274024 25280712 24 LOSS Xp21.3 67,33 26891769 26959101 25 GAIN Xp21.3 60,40 27277529 27337933 25.A LOSS Xp21.2 9,69 31282923 31292613 25.B LOSS Xp21.1 28,26 33953232 33981492 25.C GAIN Xp21.1 185,02 34931807 35116827 25.D GAIN Xp21.1 215,00 35269628 35484626 26 GAIN Xp21.1 88,57 37168387 37256960 27 GAIN Xp21.1 9,61 37242364 37251969 30 GAIN Xp11.3 81,13 47766391 47847516 31 LOSS Xp11.3 81,13 47766391 47847516 31.A GAIN Xp11.23 78,87 48021982 48100848 32 LOSS Xp11.22 4,15 52065798 52069943 33.A LOSS Xp11.21 58,89 56403390 56462278 34.A GAIN Xp11.12 48,06 56870427 56918489 35 GAIN Xp11.1 117,14 57318438 57435573 36.A GAIN Xq11 716,03 63925948 64641977 38 GAIN Xq13.2 8,98 72202996 72211976 38.A GAIN Xq13.2 192,04 74375875 74567915 38.B GAIN Xq13.3 153,23 75123387 75276621 39 GAIN Xq21.1 21,98 76992067 77014050 40 GAIN Xq21.1 5,28 80112246 80117526 49 GAIN Xq22.1 5,30 100942190 100947490 50 LOSS Xq22.1 45,36 101803578 101848935 51 GAIN Xq22.2 34,69 103152319 103187013 53.A LOSS Xq24 170,73 118278913 118449646 54 LOSS Xq24 44,85 118281024 118325874 55 GAIN Xq24 206,90 118691020 118897917 55.A GAIN Xq25 53,80 120385787 120439584 56 LOSS Xq25 86,07 124632886 124718959 57 LOSS Xq25 188,03 124929673 125117699 58 GAIN Xq25 9,68 125143278 125152957 58.A LOSS Xq25 12,68 125198109 125210792 59.A GAIN Xq26.3 24,69 134151039 134175725 60 GAIN Xq26.3 42,30 134585636 134627936 60.A LOSS Xq26.3 50,84 134801361 134852198 60.B GAIN Xq26.3 13,45 136050422 136063872 60.C GAIN Xq26.3 91,26 137089527 137180783 60.D LOSS Xq27.1 217,83 140175103 140392930 61 LOSS Xq27.2 4,67 140773893 140778561 64 LOSS Xq27.3 3,92 143436347 143440268 66 LOSS Xq27.3 7,35 145030566 145037917 66.A LOSS Xq28 37,12 147393583 147430698 67 LOSS Xq28 5,42 148456474 148461889 68 GAIN Xq28 105,66 148686631 148792286 69 LOSS Xq28 11,77 154044877 154056645 71 LOSS Xq28 290,99 154586913 154877901 71.A LOSS Xq28 122,36 154755542 154877901

Project description:BackgroundHypophosphatasia (HPP) is a rare, inherited, metabolic bone disease caused by deficient tissue-non-specific isoenzyme of alkaline phosphatase activity that manifests as a broad range of signs/symptoms, including bone mineralization defects and systemic complications. The burden of disease is poorly characterized, particularly in children. This study aimed to characterize the patient-reported burden of disease among children with HPP using two survey instruments: the HPP Impact Patient Survey (HIPS) and the HPP Outcomes Study Telephone interview (HOST).MethodsBetween September 2009 and June 2011, pediatric patients (aged younger than 18?years) with HPP were recruited to participate in the study via patient advocacy groups or their medical provider. Survey questions were used to capture information on patient demographics, HPP-related medical history, mobility, and health-related quality of life (HRQoL; using the 10-item Short-Form Health Survey for Children [SF-10], HIPS only).ResultsCommon clinical features of the 59 pediatric survey respondents (mean [standard deviation] age: 7.6 [5.1] years; 51% male) included pain (86% of patients), muscle weakness (71%), difficulty gaining weight (64%), and delayed walking (59%). Fracture was reported by 36% of patients; multiple fractures were also reported (15% of patients). Use of assistive devices for mobility was frequent among the study population (51%). In response to the SF-10, patients reported a substantial impact of HPP on their HRQoL; physical function was the most severely impaired component relative to normative data. Of patients responding to the HOST, two-thirds experienced worsening of at least one of their HPP-related signs/symptoms over a 5-year period.ConclusionsIn pediatric patients, HPP is associated with a high burden of disease and a substantial negative impact on HRQoL. The burden of HPP may increase and HRQoL reduce further over time as signs/symptoms that affect HRQoL worsen or new signs/symptoms manifest.

Project description: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.

Project description:IntroductionLittle is known about how patients with asthma and eczema perceive their medical care and burden of disease. A survey was conducted to evaluate the perceptions among the general patient population with asthma and/or eczema regarding disease and treatment burden and barriers to adequate care.MethodsAn online survey was completed by market research panelists in the USA between March 24, 2020 and April 6, 2020. Eligible participants were at least 18 years of age and endorsed a diagnosis of asthma and/or eczema. Survey responses are described for all participants, by designated racial/ethnic groups, and by income level.ResultsIn all, 841 participants completed the survey (asthma, n = 554; eczema, n = 398; both, n = 111; White, n = 421; Black, n = 252; Hispanic, n = 95; low income [less than $15,000/year], n = 99; higher income [at least $15,000/year], n = 713). More Black and Hispanic participants than White participants, and more participants with low income than higher income, endorsed health literacy as a barrier (e.g., filling out official documents, understanding written materials). Participants with low income were less likely than participants with higher income to have an asthma action plan (42% vs 53%, respectively) and to discuss asthma control with their healthcare provider (54% vs 69%). Black and Hispanic participants were more likely than White participants to have an emergency department visit (52% and 49% vs 31%, respectively) or hospitalization (31% and 39% vs 16%) for asthma within the last 12 months. Participants reporting low income indicated that they experienced eczema symptoms more frequently than participants with higher income; 35% of low-income participants vs 15% of higher-income participants reported that they had not tried any eczema treatments. Participants in all racial/ethnic and income-level groups reported that their asthma or eczema impacted their lifestyle and daily activities.ConclusionMore effective and culturally informed communication and education strategies to improve health information uptake and shared decision-making are needed to reduce the burdens of disease and treatment in highly impacted populations.

Dataset Information

The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey.

Publications

The Lifelong Impact of X-Linked Hypophosphatemia: Results From a Burden of Disease Survey.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets