A ROUTINE BLOOD TEST CAN STRONGLY

SUPPORT THE DIAGNOSIS OF HPP.1,2

Early, accurate diagnosis is critical to ensure adequate
clinical management to avoid preventable morbidities.3-5

MISDIAGNOSIS/MISMANAGEMENT

In infants, a diagnostic delay of months can be critical or life threatening 3,6

According to 2 patient-reported surveys, almost 25% of patients who

were diagnosed with HPP as adults reported experiencing symptoms
during childhood 7,a

 isdiagnosis can lead to ineffective management with vitamin D,

M
calcium supplements, or bisphosphonates all of which can exacerbate
symptoms of HPP 2-4

ACCURATE DIAGNOSIS
Low ALP in patients with clinical manifestations of HPP can strongly support
a diagnosis. 1,2

Low ALP can be identified with a commonly available,

routine blood test 1,2

ALP activity should be age-adjusted and is laboratory-specific 2

Patients with HPP typically have ALP activity below the age-adjusted
lower limit of normal 1,2

I f low ALP is identified, a diagnosis of HPP can be confirmed by testing

for elevated serum PLP or urinary PEA 2,6,8,9

HIPS/HOST combined data from an Internet questionnaire and telephone survey that queried demographics, HPP-related illness
history, disease progression, disease burden, and health-related quality of life. One hundred eighty-four patients participated
(59 children, 125 adults).7

AVOID COMMON MISDIAGNOSIS.

Patients with HPP are often misdiagnosed
because clinical presentation of HPP can overlap
with other more common skeletal disorders.1,2

 ow ALP activity and high concentrations of ALP substrates differentiate

L
HPP from other disorders and can help ensure an accurate diagnosis 1-3

LAB VALUE ASSESSMENT CAN DIFFERENTIATE HPP

FROM OTHER SKELETAL DISORDERS 1-3,10-13
DISORDER
HPP

Nutritional
rickets

X-linked
hypophosphatemic
rickets

ALP 3,10-12

Normalb

Serum PLP 13

Osteogenesis
imperfecta

Normal

Normal

Calcium 1,3,10,11

or normal

Phosphate 2,3,10,11

or normal

PTH 1,3,9,12

or normal

Normal

Normal

Vitamin D 3,9,11

Normal

or normal

Normal

Normal

Abbreviation: PTH, parathyroid hormone.

I n some cases, newborns with severe osteogenesis imperfecta (type II) can have low serum ALP activity.12

Other common misdiagnoses may include osteomalacia, chondrodysplasia

with bone-mineralization defects, osteoarthritis, osteopenia/osteoporosis,
and periodontal disease 1,2

When diagnosing bone-mineralizing disorders, looking for

HPP should be part of your protocol in order to ensure an
accurate diagnosis.

References: 1. rockman-greenberg C. Hypophosphatasia. Pediatr endocrinol rev. 2013;10(suppl 2):380-388. 2. Mornet e, nunes Me. Hypophosphatasia. in: Pagon ra, bird
Td, dolan Cr, stephen K, eds. genereviews. seattle, Wa: university of Washington, seattle; 1993. http://www.ncbi.nlm.nih.gov/books/nbK1150/. Published november 20, 2007.
updated august 5, 2010. accessed March 31, 2014. 3. Mohn a, de leonibus C, de giorgis T, Mornet e, Chiarelli F. Hypophosphatasia in a child with widened anterior fontanelle:
lessons learned from late diagnosis and incorrect treatment. acta Paediatr. 2011;100(7):e43-e46. 4. sutton ral, Mumm s, Coburn sP, ericson Kl, Whyte MP. atypical femoral
fractures during bisphosphonate exposure in adult hypophosphatasia. J bone Miner res. 2012;27(5):987-994. 5. Cundy T, Michigami T, Tachikawa K, dray M, Collins J.
Phenotypic change in a patient with hypophosphatasia with the onset of renal failure. Paper presented at: 40th annual Congress of the european Calcified Tissue society (eCTs);
May 18-21, 2013; lisbon, Portugal. 6. baumgartner-sigl s, Haberlandt e, Mumm s,et al. Pyridoxine-responsive seizures as the first symptom of infantile hypophosphatasia
caused by two novel missense mutations (c.677T>C, p.M226T; c.1112C>T, p.T371i) of the tissue-nonspecific alkaline phosphatase gene. bone. 2007;40(6):1655-1661. 7.
Champigneulle a, Whyte M, rockman-greenberg C, et al. Fracture burden in children and adults with hypophosphatasia. Poster presented at: osteologie 2014 Congress;
March 13-15, 2014; Munich, germany. 8. Whyte MP. Hypophosphatasia. in: scriver Cr, beaudet al, sly Ws, valle d, eds. The Metabolic and Molecular bases of inherited disease.
vol 4. 8th ed. new york, ny: Mcgraw-Hill; 2001:5313-5329. 9. Whyte MP, Mahuren Jd, vrabel la, Coburn sP. Markedly increased circulating pyridoxal-5-phosphate levels
in hypophosphatasia. J Clin invest. 1985;76(2):752-756. 10. nield ls, Mahajan P, Joshi a, Kamat d. rickets: not a disease of the past. am Fam Physician. 2006;74(4):619-630.
11. Carpenter To, imel ea, Holm ia, Jan de beur sM, insogna Kl. a clinicians guide to X-linked hypophosphatemia. J bone Miner res. 2011;26(7):1381-1388. 12. Whyte MP.
Hypophosphatasia. in: Thakker rv, Whyte MP, eisman Ja, igarashi T, eds. genetics of bone biology and skeletal disease. london, uK: academic Press; 2013:337-360. 13. reynolds
rd, lorenc rs, Wieczorek e, Pronicka e. extremely low serum pyridoxal 5-phosphate in children with familial hypophosphatemic rickets. am J Clin nutr. 1991;53(3):698-701.
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