Abstract
We present changes on physical therapy (PT), occupational therapy (OT), and speech-language pathology (SLP) assessments for a patient pre- and 6 months post-initiation of recombinant alkaline phosphatase therapy for hypophosphatasia (HPP).
Our patient is a 30-year-old male diagnosed with pediatric onset HPP at the age of 28. Features of his HPP include skull deformities and scoliosis noted as a toddler, early loss of primary dentition with the root intact prior to the age of 4, severe bone and muscle pain described as “severe growing pain”, and fatigue as a teenager. He was noted to have arthritis in his feet requiring surgical fusion, which was complicated by nonunion. By the age of 30, he required the use of assistive devices for ambulation due to fatigue and pain. Biochemistry was notable for ALP 17U/L (40-150), serum PLP 241 mcg/L (5-50), urine phosphethanolamine 47 nmolmgCr (0-27), and genetic testing demonstrated a variant of undetermined significance of ALPL genet (Het. C.1364G>A p.Gly455Asp).
PT and OT assessments included a thorough musculoskeletal and neurologic examination, as well as functional testing of mobility, balance, motor control, and activity of daily living tasks. After 6 months of enzyme replacement therapy (ERT), the patient’s scores on measures of body structure and function were grossly unchanged or diminished (muscle strength). However, activity-based measures of functional performance generally improved on ERT. Performance on the Five Times Sit to Stand Test (FTSTS), gait speed, Functional Gait Assessment, Sensory Organization Test, and Six-Minute Walk Test (6MWT) improved. His most significant improvements were on the FTSTS and 6MWT; his FTSTS improved from 15.4 seconds to 9.1 seconds, surpassing the cut-off for falls risk (12s), while his 6MWT improved from 1,228 feet to 1,541 feet, surpassing the minimal detectable change for individuals with osteoarthritis (201 ft).
Cognitive testing revealed improvement in delayed memory (e.g., word-list recognition, story-retell) on the Repeatable Battery of the Assessment of Neuropsychological Status from baseline (7%tile) to 6 months post therapy (47%tile). He also demonstrated improvement in Trail Making Part A [TM A, cognitive processing speed] & TM B (executive functioning) from baseline (45s, 49s) to 6 months post therapy (21s, 38s). Mean performance on TM A&B for adults 25-34 yrs is 24.4s±8.71 and 50.7s±12.4, respectively.
Overall, the patient demonstrated improvement in delayed memory, cognitive processing speed and executive functioning on ERT. Additionally, while his performance on bedside impairment-based testing generally declined or remained unchanged, his performance on standardized functional assessments improved on ERT. These functional improvements in physical and cognitive domains likely enable the patient to more fully participate in life roles to improve quality of life.
Cognitive processing speed mediates the effects of cardiovascular disease on executive functioning.
