ODP592 Delay in Diagnosis of Adult with Familial Hypophosphatasia

Abstract

Abstract Background Familial Hypophosphatasia (HPP) is a rare genetic disorder characterized by defecitve bone and/or teeth mineralization in the presence of low alkaline phosphatase activity due to loss-of-function mutations in the Alkaline Phosphatase, Biomineralization Associated (ALPL) gene. HPP typically presents in middle age with a mild phenotype. Case Presentation A 43-year-old woman with PMH undifferentiated connective tissue disease and GERD referred to endocrinology clinic. She was previously diagnosed with schleroderma and was treated with prednisone and hydroxychloroquine without symptom improvement. Symptoms included: progressing bone, joint, and muslce pain; unsteady gait; proximal muscle weakness; fatigue; early loss of deciduous teeth; loss of teeth mineralization; history of finger and toe fractures from repetitive stress. Family History: Mother: ongoing joint/muscle pain as well as tooth loss. Daughter: failure to thrive, kyphosis, orthopedic problems, required leg casting for 1 year. Physical Exam: unrevealing (limited due to video visits). Significant Laboratory/Imaging Findings: Serum alkaline phosphatase (ALP): 16 U/L (ref. 35-140 U/L)Vitamin B6: 235.3 nmol/L (ref. 20-125 nmol/UL)Calcium: 9.3 mg/dL (ref. 8.5-10.6 mg/dL).Dual energy X-ray absorptiometry (DXA): normal bone mass for age.Genetic testing: one heterozygous pathogenic variant in ALPL, c.318G>C (p.CIn106His). Treatment Course: Genetic testing consistent with a diagnosis of familial HPP, specifically juvenile onset. Initiated on Asfotase-alfa, an alkaline phosphatase enzyme replacement therapy. Screening prior to treatment: Renal ultrasonography without ectopic calcificationOpthalmology exam without calficiations identified Discussion HPP should be suspected in patients with defective mineralization of bone and/or teeth in the setting of an unexplained low serum ALP activity and elevated Vitamin B6 level. Non-specific symptoms such as bone, joint, and muscle pain are common presenting symptoms in adults with HPP. Treatment with asfotase-alfa may be considered for adults with symptom onset in childhood, including early loss of deciduous teeth. Early diagnosis and treatment may improve overall quality of life. At this time, there are no guidelines for selecting adult patients for treatment with alfoterase-alfa. Further studies are needed to evaluate the benefits of enzyme replacement therapy among adults with HPP. Presentation: No date and time listed