Rare, Genetic Form of Rickets Treated at Shriners Hospital

From the time he was born, 5-year-old Matthew Arron Smith was an uncommon child.

"He was uncommonly bright, uncommonly outgoing, and he had a very uncommon disease," said his mother, Leticia Chavez-Smith.

At age 2, Matthew was diagnosed by a geneticist with X-linked hypophosphatemic rickets, a rare form of rickets that affects one in 20,000 individuals and causes excessive bowing of the legs.

Matthew has been a patient at Shriners Hospital for Children in the Texas Medical Center for the past two years, and prior to that, was treated at Shriner’s Sacramento hospital when his family lived in California.

"When Matthew was first seen, his legs made a complete U-shape because he was so bowed," said Leticia. "His medication therapy and the braces have improved the shape of his legs."

Children with X-linked hypophosphatemic rickets who are referred to and accepted for treatment by Shriners Hospital are seen at the hospital’s monthly metabolic clinic, headed by pediatric endocrinologist Dr. Patrick Brosnan and orthopedic surgeon Dr. Byron York.

X-linked hypophosphatemic rickets is a genetic condition. "Hypophosphatemic" means there is a deficiency of phosphates in the blood due to excessive excretion of phosphates in the urine. The physical signs of rickets are present, including bowed or knock-kneed legs. However, unlike most other forms of rickets, the calcium levels of patients with X-linked hypophosphatemic rickets are usually normal.

"Patients with this disorder show the clinical features of rickets, including short stature, bowing of the legs, and radiographic evidence of poor bone mineralization, but with variable severity," explained Dr. Brosnan.

Patients also have a problem assimilating and using calcium and phosphorus due to inadequate activation of vitamin D, which results in soft and deformed bones.

If inadequately treated in childhood, a middle-aged patient often experiences painful cracks in bones, osteoarthritis brought on by premature wear in the knees and hips, and calcification in the membranes around the joints and between bones. Dental problems, particularly unexplained abscesses in primary teeth, also are a common sign of the disease.

Typically, if there is no known family history, parents become concerned when a toddler’s legs appear bowed. The diagnosis can be difficult to establish, but blood tests and radiographs may show an elevated alkaline phosphatase and profoundly low phosphorus levels.

X-linked hypophosphatemic rickets is genetically transmitted due to a defect carried on the X, or female, chromosome. The condition is passed from affected fathers, to all of their daughters, but none of their sons, or from affected mothers with a 50 percent risk to their children of either gender.

In Matthew’s case, his mother had the disease and passed it on to her son. However, his 11-year-old sister Angela and 4-year-old brother Joseph did not inherit the condition.

"I always had problems with my hips and knees, but I had no idea that I had this condition until after Matthew was born," said Leticia. "Matthew is not very affected by his condition and is extremely bright. Absolutely nothing holds him back – even his leg braces don’t stop him."

Currently, the treatment for X-linked hypophosphatemic rickets consists of phosphorus and activated vitamin D (calcitrol) by mouth. Because the loss of phosphorus in the urine is quite fast, it needs to be replaced frequently, about four or five times a day. Initially, the daily doses of phosphorus and activated vitamin D are based on body weight – about 70 milligrams per kilogram of body weight for phosphorus and 20 nanograms per kilogram of body weight for calcitrol.

Further adjustments in medication dosages are made as patients grow, Dr. Brosnan said.

By making the bones stronger, treatment can prohibit the bones from bending and make braces unnecessary. Children treated for the condition at Shriners are evaluated every four months for height, weight, labs and possibly X-rays of the legs and/or the arms to check the bones’ response to medication. Maintaining a normal weight is important because any additional weight can cause stress on already weakened bones.

Early detection is a key to successful treatment, and children treated before walking age have the best chance for recovery, Dr. Brosnan said.

"The sooner children are diagnosed and treated, the better odds they will have."

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©2006 Texas Medical Center

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