Abstract #1173335: Delayed Diagnosis of Juvenile Hypophosphatasia

Abstract

Hypophosphatemia, a rare inherited disorder is characterized by defective mineralization of bone and/or teeth as well as the presence of low activity of serum and bone alkaline phosphatase. Affected individuals are often unrecognized or misdiagnosed. A 48-year-old female of European descent presented to endocrinology with a long history of stress fractures of various extremities and dental issues with loose teeth. Past medical history was significant for benign positional vertigo, perimenopause, nasal cartilage collapse and post-traumatic stress disorder. Past surgical history included four bone grafts. Family history was notable for mother with early adulthood hip fracture and osteoporosis. She denies any use of tobacco products, alcohol, and does not exercise regularly due to pain and limited range of motion. Physical examinations showed no noted abnormalities other than diffuse muscle and joint pain. Dental examination demonstrated loose teeth of both upper and lower jaws, which were confirmed on X-rays. Laboratory findings: serum alkaline phosphatase level 21 U/L (normal 35-113), normal renal, PTH and thyroid function tests. Cone beam CT scan showed edentulous maxilla, thin cortical contours, sclerotic cancellous bone surrounding the teeth and bone loss of mandibular teeth. Baseline dual-energy x-ray absorptiometry was normal. A genetic testing due to concern for hypophosphatasia revealed a single heterozygous pathogenic variant in the ALPL gene. Hypophosphatasia can cause several skeletal abnormalities in affected infants such as short limbs, soft skull bones and unusual chest shape. Other complications that have been noted in affected infants include hypercalcemia, respiratory problems and difficulty in gaining weight. Early primary tooth loss is one of the first signs of this condition in children, which was the case with our patient. Adult forms of this condition may present with recurring fractures, chronic pain and premature tooth loss of the secondary set of teeth, as reported in our patient. A low total serum alkaline phosphatase is a hallmark of this disease. Also elevated serum pyridoxal-5-phosphate and elevated urinary phosphoethanolamine support the diagnosis. Hypophosphatasia can be treated with recombinant human alkaline phosphatase (Asfotase alfa StrensiqTM), which has been proven to improve respiratory and motor functions, bone mineralization and reduce tooth loss and our patient is currently on this treatment. This case highlights the importance of early diagnosis of hypophosphatasia in adults and appropriate treatment to prevent further complications.