How many more doors will patients need to
knock on to get accurately diagnosed?
knock on to get accurately diagnosed?
Observational study in children (n=121) and adults (n=148) enrolled in the Global HPP Registry; diagnostic delay in adults (n=52) was reported as the age at earliest reported manifestation vs age of diagnosis of HPP.2
Signs and symptoms of HPP can appear at any age and often resemble more common conditions, such as3-13:
- osteoporosis
- arthritis
- fibromyalgia
- pseudogout
- other rheumatic conditions
The impact of deficient alkaline phosphatase (ALP) activity in HPP can be significant. Early detection and assessment of disease burden may help avoid7,14-17:
If you see an ALP value of ~40 U/L or below† in adults or ~160 U/L or below†‡ in children, look for a pattern of persistently low levels adjusted for patient age and sex.1,20-26
*Persistently low ALP can be defined as 2 or more ALP levels below normal range in intervals of more than 30 days.1,14,25,27
†These values serve as general guidelines to prompt further investigation; however, evaluation should always be based on persistently low readings relative to the specific age- and sex-adjusted reference ranges of the performing laboratory.28
‡The value of ~160 U/L or below is based on the Associated Regional and University Pathologists (ARUP) Reference Laboratory (Utah, USA) online test directory being the highest level of the low range of ALP for male and female patients aged 1-9 years old. It is important to note that normal ranges for serum ALP activity are higher in infants, children, and adolescents than they are in adults. These values serve as general guidelines to prompt further investigation; however, evaluation should always be based on persistently low readings relative to the specific age- and sex-adjusted reference ranges of the performing laboratory.23,24
Note: An ALP level of <40 U/L is not conclusive for a diagnosis of HPP. Refer to your lab for appropriate age- and sex-adjusted reference ranges.
Note: The value of 160 U/L can be used to screen for HPP and should not be considered a diagnostic marker for pediatric patients.
Age- and sex-adjusted ALP reference ranges (U/L)24§
yr, year.
Note: graph adapted from Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project (Colantonio DA, et al. 2012). CALIPER samples from 1072 male and 1116 female participants (newborn to 18 years) were used to calculate age- and sex-specific reference intervals. No variations in ALP based on ethnic differences were observed.24
§ALP ranges must be age- and sex-adjusted. Patients should be evaluated for other symptoms of HPP, and differential diagnoses should be ruled out.1,3,10,12,25,29-34
Note: graph adapted from Canadian Laboratory Initiative on Pediatric Reference Intervals (CALIPER) project (Colantonio DA, et al. 2012). CALIPER samples from 1072 male and 1116 female participants (newborn to 18 years) were used to calculate age- and sex-specific reference intervals. No variations in ALP based on ethnic differences were observed.24
To diagnose HPP, look for persistently lowII ALP alongside clinical signs and symptoms, such as impaired physical function, musculoskeletal and joint pain, bone fractures, or chronic fatigue.1,3,10,12,14,25,29-34
IIPersistently low ALP can be defined as 2 or more ALP levels below normal range, adjusted for patient age and sex, in intervals of more than 30 days.1,14,25,27
Suggested framework for diagnosing a patient with suspected HPP1,25
Since HPP can be inherited, a diagnosis should prompt ALP testing and evaluation of any signs or symptoms in the patient’s family.17,25,36
While a positive ALPL genetic test may help to confirm if your patient has HPP, it is NOT required for diagnosis, and a negative test does not rule out HPP38
Possible test results
A clinical geneticist is recommended to interpret results and understand if other family members may be affected.
These are not all possible genetic test results.
According to the latest update of the Leiden Open Variation Database (LOVD) website (https://databases.lovd.nl/shared/genes/ALPL), more than 500 unique loss-of-function variants of the ALPL gene have been described to date. However, this number is consistently being updated.
#Patients with a clinical diagnosis of HPP who were negative for ALPL variants have been reported.17
We honor the life and work of Dr Deal, whose expertise and contributions continue to make an impact on the HPP community.
Once I was diagnosed with HPP, the puzzle pieces started to fall into place, especially the fact that my muscles are weaker and my joints hurt.
— CAROL, living with HPP
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