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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 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)
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.