XLH Prevalence in Paraná, Brazil, Lower Than Elsewhere in World, Study Finds

The prevalence of X-linked hypophosphatemia (XLH) in the Brazilian state of Paraná is lower than elsewhere in the world, at about five cases per million inhabitants, according to a new study.

This is the first study to estimate the prevalence of XLH in Latin America, and it indicates that a national registry in Brazil for rare diseases such as XLH could aid in further epidemiological research, the investigators said.

The study, “Prevalence and clinical characteristics of X-linked hypophosphatemia in Paraná, southern Brazil,” was published in Archives of Endocrinology and Metabolism. The study received financial support from the pharmaceutical company Ultragenyx, a developer of the XLH treatment Crysvita (burosumab).

XLH is caused by mutations in the gene PHEX. These mutations lead to low levels of phosphate in the body, ultimately resulting in symptoms such as bone abnormalities and muscle weakness and pain.

In European and Asian countries, the prevalence of XLH has been reported to range between 16 and 48 cases per million individuals — though notably, most research has focused on children and adolescents, rather than the total population. In contrast, no studies at all have assessed the prevalence of XLH in Latin America.

Intending to address this knowledge gap, researchers in Brazil analyzed the prevalence of XLH in a defined geographic region in Latin America, namely the entire state of Paraná, located in southern Brazil.

The team surveyed 244 specialty doctors — mostly endocrinologists (68%), or doctors who treat diseases related to problems with hormones — in Paraná during 2018. Of the respondents, 18 reported caring for people with XLH. Three additional XLH patients were identified by assessing public databases. Notably, a potential limitation of the study is the possibility of missed cases from the nearly 90% specialists who did not respond to the survey, the scientists said.

“A registry of all cases of XLH and other rare diseases, following the model of certain European countries, is an important shortcoming of the Brazilian health care system that deserves more attention,” the team wrote.

“This strategy would improve the collection of epidemiological data on rare diseases in our country,” the scientists wrote.

Overall, the study identified 57 people with XLH living in Paraná, corresponding to a prevalence of roughly five cases per million people. A sub-analysis including only children and adolescents (ages 19 and younger) estimated the prevalence at 7.8 cases per million inhabitants.

“This prevalence is low compared with the rates reported in other studies from Denmark, Japan, and Norway, which range from 16 to 48 per million inhabitants,” the researchers concluded. However, they also noted that their study “found a lower prevalence than this in a subanalysis restricted to individuals aged 19 years or below.”

Of the 57 patients identified, the median age was 22 years (range 1–55 years), with 42.2% younger than age 18. A majority (60.5%) were female, and 65.4% had a family history of XLH.

The most common disease manifestation was lower limb deformity, present in 52 (91.2%) of patients. Fragility fractures — broken bones after falls from a short height — were reported in 16 patients (28.1%), and chronic kidney problems were reported in 11 (19.3%).

Most (90%) of the patients received some form of conventional treatment, such as phosphate or calcium supplements. None were treated with Crysvita.

A further analysis of 19 patients treated at Hospital de Clínicas at Universidade Federal do Paraná provided further details. Genetic testing in this group revealed a previously unreported mutation in the PHEX gene.