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Assess your patient's alkaline phosphatase levels
Persistently low alkaline phosphatase (ALP) is the biochemical
hallmark of hypophosphatasia1-3
Compare your patient’s current and historical ALP levels from their
comprehensive metabolic panel against normal age- and sex-adjusted
reference ranges.
Based on the age- and sex-adjusted reference range4-8
ALP Activity (U/L)
null
100
100
High = over 369 U/L
Normal = 156-369 U/L
Low = under 156 U/L
Limitations: A low ALP value is not conclusive for diagnosis of
HPP. Patient should be evaluated for other symptoms of HPP and
differential diagnoses should be ruled out. Check with your lab
for their appropriate age- and sex- adjusted reference ranges.7
Persistently low age- and sex-adjusted ALP is the
biochemical hallmark of HPP.1,2 Paired with key signs and symptoms, persistently low ALP can confirm
a diagnosis of HPP. Be sure to check your patient’s prior comprehensive
metabolic panel results to assess historical ALP levels.1-3
After reviewing this information, how confident are you in
considering a diagnosis of HPP in patients with perplexing
symptoms and persistently low age- and sex-adjusted ALP?
NOTE: Reference range was taken from the Canadian Laboratory
Initiative on Pediatric Reference Intervals (CALIPER) Database
which compiled age- and sex-specific reference intervals in a
pediatric population.3
*Clinicians should ensure that reported laboratory results for
ALP reflect age- and sex-adjusted reference ranges for the
specific patient.
Check with your lab for their appropriate age- and sex- adjusted
reference range.
This resource is for educational purposes only. It is not
intended for use in diagnosis of any disease or condition or for
the cure, mitigation, or treatment of any disease or condition.
It does not replace a healthcare professional’s judgment or
clinical diagnosis.
References:1. McKiernan FE, Berg RL, Fuehrer J. Clinical
and radiographic findings in adults with persistent hypophosphatasemia.
J Bone Miner Res. 2014;29(7):1651-1660.
2.Bianchi ML. Hypophosphatasia: an overview
of the disease and its treatment. Osteoporos Int.
2015;26(12):2743-2757.
3. Kishnani PS, Rockman-Greenberg C, Rauch F,
et al. Five-year efficacy and safety of asfotase alfa therapy
for adults and adolescents with hypophosphatasia. Bone. 2019;121:149-162.
4. Adeli K, Higgins V, Nieuwesteeg M, et al.
Biochemical marker reference values across pediatric, adult,
and geriatric ages: establishment of robust pediatric and adult
reference intervals on the basis of the Canadian Health Measures
Survey. Clin Chem. 2015;61(8):1049-1062.
5. ARUP Laboratories. Alkaline phosphatase isoenzymes,
serum or plasma. Accessed March 30, 2023. https://ltd.aruplab.com/Tests/Pub/00210206. Rockman-Greenberg C. Hypophosphatasia. Pediatr
Endocrinol Rev. 2013;10(suppl 2):380-388.
7. Bishop N, Munns CF, Ozono K. Transformative
therapy in hypophosphatasia. Arch Dis Child. 2016;101(6):514-515.
8. Colantonio DA, Kyriakopoulou L, Chan MK,
et al. Closing the gaps in pediatric laboratory reference intervals:
a CALIPER database of 40 biochemical markers in a healthy and
multiethnic population of children. Clin Chem. 2012;58(5):854-868.
Patient case file
A 65-year-old female with chronic bone pain and no history of
fractures has gone undiagnosed since childhood. Does Betty’s
file remind you of any of your current patients?
Betty
65
F
medical history
Reports chronic pain, fatigue, and a history of
depression
Age 54: Diagnosed with osteoporosis
Taking bone agent for ~11 years with periodic
treatment breaks and no change in bone mineral
density
family History
Father: Osteoporosis
Sibling: Osteoporosis with atypical femoral
fracture, prescribed bisphosphonates
presenting symptoms
Bone pain
Fatigue
Abnormal gait
current medications
Taking bone agent for ~11 years with periodic
treatment breaks
Reports of self-medicating daily with NSAIDs
Lab results/Imaging
CMP test results from:
Today
TEST
RESULT
FLAG
Calcium, mg/dL
8.6
Protein, g/dL
7.3
Albumin, g/dL
3.8
Alkaline phosphatase, IU/L
23
1 year ago
TEST
RESULT
FLAG
Calcium, mg/dL
9.9
Protein, g/dL
7.1
Albumin, g/dL
4.7
Alkaline phosphatase, IU/L
24
TEST
RESULT
FLAG
Calcium, mg/dL
9.2
Protein, g/dL
6.9
Albumin, g/dL
3.6
Alkaline phosphatase, IU/L
26
High vitamin B6 level shown at test 1
year ago and today
X-ray of right hip osteoporosis, age 54
DEXA result summary of right hip, age 65
DEXA result summary of right hip, age 54
DEXA result summary of lumbar spine, age
65
DEXA result summary of lumbar spine, age
54
physician notes
Referred by podiatrist to orthopedist for chronic
foot pain
No fracture found on imaging
A 57-year-old male has gone undiagnosed for 30+ years. Does
Nathan’s file remind you of any of your current patients?
Nathan
57
M
medical history
2 nontraumatic fractures: Age 13, femur; age 16,
metatarsals
Reports of slow healing fractures, even at young
age
Age 50: Kidney stones
History of poor dentition and weak/loose teeth
Recent diagnosis of
pseudogout/CPPD/chondrocalcinosis
family History
Mother: Osteoporosis
Father: Hypertension, myocardial infarction at 67
presenting symptoms
Bone pain in back and thighs
Chronic fatigue
Current nontraumatic hairline fracture
Reports of anxiety and depressed mood
current medications
Uses over-the-counter calcium and vitamin D
supplements daily (not physician-directed)
Reports of self-medicating daily with NSAIDs
Lab results/Imaging
CMP test results from:
Today
TEST
RESULT
FLAG
Calcium, mg/dL
10.6
High
Protein, g/dL
6.5
Albumin, g/dL
4.6
Alkaline phosphatase, IU/L
63
6 months ago
TEST
RESULT
FLAG
Calcium, mg/dL
9.8
Protein, g/dL
6.9
Albumin, g/dL
3.9
Alkaline phosphatase, IU/L
35
1 year ago
TEST
RESULT
FLAG
Calcium, mg/dL
10.2
Protein, g/dL
7.1
Albumin, g/dL
4.0
Alkaline phosphatase, IU/L
32
High vitamin B6 level shown at test 6
months ago
ALPL genetic
test: Variant of uncertain significance (VUS)
identified
Femur fracture
age 13
Metatarsal fracture
age 16
Tibial fracture
age 57
physician notes
N/A
A 35-year-old female born prematurely. Does Anna’s file remind
you of any of your current patients?
Hydrocodone taken as needed for severe pain
episodes
Lab results/Imaging
CMP test results from:
Today
TEST
RESULT
FLAG
Calcium, mg/dL
9.9
Protein, g/dL
7.1
Albumin, g/dL
4.1
Alkaline phosphatase, IU/L
34
3 months ago
TEST
RESULT
FLAG
Calcium, mg/dL
9.8
Protein, g/dL
7.5
Albumin, g/dL
4.2
Alkaline phosphatase, IU/L
29
Radiograph showing enlarged pulp
chambers and shape abnormalities.
Dental manifestations of
hypophosphatasia in children and the
effects of enzyme replacement therapy
on dental status: A series of clinical
cases
by Larisa Kiselnikova is licensed under
CC BY 4.0.
Early loss of baby teeth with root
intact
physician notes
Patient has an executed “pain contract” with
physician's office due to history of opioid use
A 7-year-old female with ALP levels of 138. Does Hannah’s file
remind you of any of your current patients?
Hannah
7
F
medical history
Age 4: History of nontraumatic tooth loss
Delay in walking milestone
Age 5: Bout with streptococcal pharyngitis,
treated with antibiotics
History of early tooth loss, delayed eruption
of permanent teeth, and chronic pain
Father: No significant medical history to report
Nontraumatic tooth loss at age 4
Dental manifestations of hypophosphatasia in
children and the effects of enzyme replacement
therapy on dental status: A series of clinical
cases
by Larisa Kiselnikova is licensed under
CC BY 4.0.
presenting symptoms
Short stature
Mild knock knees
Tired for past 3 months
Struggling to keep up with peers in sports/outdoor
activities
Impaired gait/mobility
Difficulty sleeping
current medications
None
Lab results/Imaging
CMP test results from:
Today
TEST
RESULT
FLAG
Calcium, mg/dL
9.3
Protein, g/dL
7.9
Albumin, g/dL
4.2
Alkaline phosphatase, IU/L
138
1 year ago
TEST
RESULT
FLAG
Calcium, mg/dL
9.1
Protein, g/dL
8.1
Albumin, g/dL
4.2
Alkaline phosphatase, IU/L
130
Currently presents with mild knock knees
Mild knock knees
Nontraumatic tooth loss at age 4
Dental manifestations of hypophosphatasia in
children and the effects of enzyme replacement
therapy on dental status: A series of clinical
cases
by Larisa Kiselnikova is licensed under
CC BY 4.0.
physician notes
N/A
A 7-month-old female with vitamin B-responsive seizures at
birth. Does Sarah’s file remind you of any of your current
patients?
Sarah
7 mo
F
medical history
Vitamin B-responsive seizures at birth
History of craniosynostosis--corrective measures
taken at 3 months
family History
Mother: No significant medical history
Father: No significant medical history
Siblings: 2 older siblings with no remarkable
medical history (ages 4 and 10 years)
A 65-year-old female with chronic bone pain and no history
of fractures has gone undiagnosed since childhood. Does
Betty’s file remind you of any of your current patients?
Medical History
Reports chronic pain, fatigue, and a history of
depression
Age 54: Diagnosed with osteoporosis
Taking bone agent for ~11 years with periodic treatment
breaks and no change in bone mineral density
Family History
Father: Osteoporosis
Sibling: Osteoporosis with atypical femoral fracture,
prescribed bisphosphonates
Presenting Symptoms
Bone pain
Fatigue
Abnormal gait
Current Medications
Taking bone agent for ~11 years with periodic treatment
breaks
Radiograph showing enlarged pulp chambers and
shape abnormalities.
Dental manifestations of hypophosphatasia
in children and the effects of enzyme
replacement therapy on dental status: A
series of clinical cases
by Larisa Kiselnikova is licensed under
CC BY 4.0.
Early loss of baby teeth with
root intact
Physician Notes
Patient has an executed “pain contract” with
physician's office due to history of opioid use
History of early tooth loss, delayed eruption
of permanent teeth, and chronic pain
Father: No significant medical history to report
Nontraumatic tooth loss at age 4
Dental manifestations of hypophosphatasia
in children and the effects of enzyme
replacement therapy on dental status: A
series of clinical cases
by Larisa Kiselnikova is licensed under
CC BY 4.0.
Presenting Symptoms
Short stature
Mild knock knees
Tired for past 3 months
Struggling to keep up with peers in sports/outdoor
activities
Dental manifestations of hypophosphatasia
in children and the effects of enzyme
replacement therapy on dental status: A
series of clinical cases
by Larisa Kiselnikova is licensed under
CC BY 4.0.
