Newly Identified Mutation Linked to XLH in Young Girl

A newly identified mutation is the probable cause of X-linked hypophosphatemia (XLH) in a young girl, according to recent case report.

The study, “X-linked hypophosphatemic rickets: a new mutation,” was published in the Brazilian Journal of Nephrology.

XLH is caused by mutations in the gene PHEX, which ultimately result in low levels of phosphate in the body, or hypophosphatemia. Since phosphate is important for proper bone growth, this can result in rickets-like symptoms, such as bowed legs and short stature.

Currently, over 500 different XLH-causing mutations in PHEX have been described. Understanding the exact mutation that causes a person’s disease may help in establishing a prognosis, as the severity of XLH is typically variable.

A team at Hospital Dona Estefânia, in Portugal, described the case of a 4-year-old girl who had experienced abnormally little growth since her first year of life. By 18 months of age, she had bowed legs.

Laboratory analyses of the patient’s blood revealed low phosphate levels, mild elevation of the parathyroid hormone, as well as high levels of alkaline phosphatase, a marker of liver damage.

Radiological examination revealed deformities in the her femur (thigh bone) and radius, found in the forearm.

Based on these findings, the patient was diagnosed with phosphopenic rickets, meaning rickets due to hypophosphatemia. She was started on vitamin D (calcitriol) and phosphate supplements.

“Currently, at 11 years old, the patient has no clinical or radiographic signs of rickets,” the researchers wrote, adding that her height has also increased significantly to its target level.

Genetic analysis revealed a heterozygous mutation in the PHEX gene — that is, a mutation in one of the two gene copies, one copy inherited from each biological parent. The specific mutation, known as c.767_768del or p.Thr256Serfs*7, had never been reported in published studies.

Subsequent analysis indicated that this is a nonsense mutation, which means that it results in a premature stop in the conversion of DNA to RNA that ultimately leads to a shorter and improperly working protein. This is a known genetic alteration in XLH, which makes this mutation likely disease-causing, the team said.

“In conclusion we report a novel, likely pathogenic [disease-casuing], variant in PHEX gene in a girl with clinical, laboratory, and radiological findings of rickets,” the investigators added.