A 26-Year-Old Woman Who Uses a Walking Cane Because of Pain

Ricardo Correa, MD; Gauri Behari, MD


September 13, 2019

The forms of hypophosphatasia that appear in childhood or adulthood are typically less severe than those that appear in infancy. Early loss of primary (baby) teeth is one of the first signs of the condition in children. Affected children may have short stature with bowed legs or knock knees, enlarged wrist and ankle joints, and an abnormal skull shape. Adult forms of hypophosphatasia are characterized by osteomalacia. In adults, recurrent fractures in the foot and thigh bones can lead to chronic pain.[6] Affected adults may lose their secondary (adult) teeth prematurely, as was the case with the patient described here. They are also at increased risk for joint pain and inflammation, again as experienced by the patient in this case.

The mildest form of this condition, called "odontohypophosphatasia," affects only the teeth. People with this disorder typically experience abnormal tooth development and premature tooth loss but do not have the skeletal abnormalities seen in other forms of hypophosphatasia.[5]

The clinical presentation of hypophosphatasia varies from devastating prenatal intrauterine disease to mild manifestations in adulthood. Six clinical forms are identified: perinatal, prenatal benign (with spontaneous improvement of skeletal defects despite prenatal signs of disease), infantile, juvenile, adult, and odontohypophosphatasia.[7]

Adults present with early loss of primary or secondary teeth, osteoporosis, bone pain, chondrocalcinosis, chronic muscle pain, reduced muscular strength, and fractures. Joint pain and restricted range of motion may be associated because of chondrocalcinosis.[6]

The diagnosis is made on the basis of history and physical examination findings, as well as laboratory tests and imaging, and is confirmed with the use of genetic analysis for the ALPL gene mutations in controversial cases.[7,8] Asymptomatic adult patients are not uncommon; in these cases, the diagnosis is made using laboratory findings, including elevated levels of vitamin B6 and its metabolite in the urine and low ALP levels.[9]

In this case, X-linked hypophosphatemia was ruled out because it occurs mostly in younger men. It is an X-linked dominant form of osteomalacia that differs from most cases of rickets in that vitamin D supplementation does not cure the condition. It can cause bone deformity, including short stature and genu varum (bow-leggedness).

Vitamin D deficiency is defined as a level < 20 ng/mL. Because this patient had a level of 52 ng/mL, it was ruled out.

Osteogenesis imperfecta is a genetic bone disorder characterized by fragile bones that easily break. It is also known as "brittle bone disease." The term literally means "bone that is imperfectly made from the beginning of life." A person born with this disorder is affected throughout his or her lifetime. The patient in this case was in her mid-20s when the symptoms first began. In addition, osteogenesis imperfecta is not associated with elevated vitamin B6 levels.


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