Related Experiment Video
Updated: Jul 12, 2026
08:42
Skeletal Phenotype Analysis of a Conditional Stat3 Deletion Mouse Model
Published on: July 3, 2020
Insight into Natural History and Phenotype in Untreated Adults with X-Linked Hypophosphatemia
Giampiero I Baroncelli1, Filomena Cetani2, Benedetta Toschi3
1Pediatric and Adolescent Endocrinology, Division of Pediatrics, Department of Obstetrics, Gynecology and Pediatrics, University Hospital, Pisa, Italy.
Calcified Tissue International
|July 10, 2026
Summary
X-linked hypophosphatemia (XLH) in adults causes severe short stature, skeletal deformities, and poor quality of life, particularly in men. This study highlights the significant impact of XLH on untreated adults, emphasizing the need for effective management strategies.
Area of Science:
- Genetics and Endocrinology
- Metabolic Bone Diseases
Background:
- X-linked hypophosphatemia (XLH) is a rare genetic disorder caused by PHEX gene mutations, leading to excess fibroblast growth factor 23 (FGF23).
- This excess FGF23 causes renal phosphate wasting and reduced vitamin D production, resulting in hypophosphatemia and rickets/osteomalacia.
Purpose of the Study:
- To investigate the natural history and phenotype of untreated adult patients with X-linked hypophosphatemia.
- To examine clinical, biochemical, skeletal features, comorbidities, and patient-reported outcomes (PROs) in this population.
Main Methods:
- A study involving 52 adult patients (mean age 51.5 years) with XLH who were not receiving phosphate supplements, active vitamin D, or burosumab.
- Assessment included clinical evaluations, biochemical markers (FGF23, bone turnover markers), skeletal imaging, and PROs.
Main Results:
- Adults with XLH exhibited severe short stature (lower Z-scores in men), overweight/obesity, significant skeletal deformities, and dental issues.
- Men showed more compromised stature and higher bone turnover markers (FGF23, osteocalcin, PINP, CTX, BALP) compared to women.
- Patient-reported outcomes indicated moderate to severe symptoms affecting quality of life, with no significant sex-based differences.
Conclusions:
- The adult XLH phenotype is characterized by severe short stature, obesity, skeletal deformities, pain, dental problems, and reduced quality of life.
- Men with XLH present with more severe skeletal and biochemicalcompromises than women.
- Findings underscore the substantial burden of XLH in untreated adults and suggest potential sex-based differences in disease manifestation.
Related Concept Videos
01:43Sex-linked Disorders
Like autosomes, sex chromosomes contain a variety of genes necessary for normal body function. When a mutation in one of these genes results in biological deficits, the disorder is considered sex-linked.
01:35Pedigree Analysis
Overview
01:19X-linked Traits
In most mammalian species, females have two X sex chromosomes and males have an X and Y. As a result, mutations on the X chromosome in females may be masked by the presence of a normal allele on the second X. In contrast, a mutation on the X chromosome in males more often causes observable biological defects, as there is no normal X to compensate. Trait variations arising from mutations on the X chromosome are called “X-linked”.
01:20Inborn Errors of Metabolism
Phenylketonuria (PKU) is a protein metabolism disorder characterized by high blood levels of the amino acid phenylalanine. This results from a mutation in the gene responsible for phenylalanine hydroxylase, an enzyme that converts phenylalanine into tyrosine. When this enzyme is deficient, phenylalanine builds up in the blood, leading to symptoms such as vomiting, rashes, seizures, growth deficiency, and severe mental retardation. An early diagnosis and a diet restricting phenylalanine intake...
02:41Lethal Alleles
Agouti: A Lethal Allele
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
Lucien Cuénot discovered lethal alleles in 1905 while studying the inheritance of coat color in mice. The agouti gene is responsible for the color of the coat in mice. This gene codes for an agouti-signaling protein, which is responsible for melanin distribution in mammals. The wild-type allele gives rise to gray-brown coat color in mice, while the mutant allele gives rise to yellow coat color. In addition to coat color, the agouti gene is associated with the yellow...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...