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Manifestations of hypophosphatasia (HPP) may be hidden below the surface.1-3

Visible symptoms:

Bone, muscle, or joint pain1,4,5
Short stature1,9
Impaired mobility1,10

Potential hidden symptoms:

Skeletal demineralization2
Stress fractures11,12
Osteopenia/ osteoporosis1,14
Calcium pyrophosphate dihydrate (CPPD) deposition disease1,15,16
Limited ability to perform everyday activities10
Decreased quality of life17

Baseline assessment, along with medical and family histories, can uncover hidden manifestations of hypophosphatasia. 1-3,14

Patients may not be aware that current and past symptoms could be caused by hypophosphatasia.3

Select appropriate tests/assessments from the following (not all are required):

Possible hidden manifestations

Tests and assessments to consider


Skeletal deformities1

Stress fractures11,12


Progressive demineralization / rickets / osteopenia / osteoporosis1,2,14


History of fractures and / or skeletal surgeries 6-8



Complete skeletal survey 2

Sequential radiographs 10


History / record review

Pain and muscle weakness

Bone pain1

Muscle pain1,4

Joint pain5

Muscle weakness1,4,10


Standardized pain assessment tool (eg, BPI, NIPS)10,18

Medication use review (current / past / increasing use of analgesics) 10


History/record review 10




Kidney stones10

Progressive renal impairment 2,22,23

Laboratory testing (eg, urinary calcium, serum creatinine) 1,10,14

Renal ultrasound10

History/record review 10


Premature tooth loss 1,24,25

Abnormal dentition1

Dental cavities14,26

Periodontal disease 27,28

Complete dental examination and history 1

Growth / development

Failure to thrive1

Short stature1,9

Missed motor milestones / delayed motor development1,4,29

Developmental assessment (eg, DDST) 10

History/record review

Physical function and quality of life

Impaired mobility1,10

Abnormal or waddling gait 1,4,10

Reduced ability to perform normal everyday activities10

Pain or unusual fatigue following gentle exercise or mild exertion 10,30,31

Impaired quality of life 17

Mobility assessment (eg, 6MWT, BOT-2) 10

Gait assessment32

Standardized, age-appropriate quality-of-life assessment tool (eg, SF-36, PedsQL, EuroQoL EQ-5D-5L) 33

Patient discussion10

Medicine use review (eg, antidepressants, anti-anxiety) 10

Abbreviations: 6MWT, 6-minute walk test; BOT-2, Bruininks-Oseretsky Test of Motor Proficiency; BPI, Brief Pain Inventory; DDST, Denver Developmental Screening Test; DXA, dual-energy X-ray absorptiometry; HHD, handheld dynamometry; NIPS, Neonatal Infant Pain Scale; PedsQL, Pediatric Quality of Life Inventory; SF-36, 36-item Short Form Health Survey.

A physical or occupational therapist can help evaluate and/or assist with the management of the patient’s physical function and disability.14,32

Detailed patient discussions are critical to uncovering the full daily impact of hypophosphatasia.

Patients may not realize the extent of their limitations or may not connect them to hypophosphatasia.

To uncover the full daily impact of hypophosphatasia, ask your patients about the following:

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  • Limited mobility
  • Pain and muscle weakness
  • Difficulty with everyday activities
  • Problems with work or school
  • Family or social challenges
Difficulty making friends or participating in activities with similarly aged peers 10
Depression or anxiety10

Clinical symptoms

Prominent clinical symptoms of hypophosphatasia

Regular follow-up evaluations are recommended, as symptoms may appear or worsen at any time.1,17,35,36
Comprehensive clinical assessment and patient history are necessary to evaluate the full impact of hypophosphatasia.1-3
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