Clinical spectrum of hypophosphatasia diagnosed in adults

Kathryn E. Berkseth, Peter Tebben, Matthew M Drake, Theresa E. Hefferan, Donna E. Jewison, Robert A. Wermers

Research output: Contribution to journalArticle

59 Citations (Scopus)

Abstract

The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age ≥ 18. years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49. years; 68% women). Most patients (68%) were symptomatic at presentation with features including musculoskeletal pain (41%) or incident fracture (18%). A history of fracture was present in 54%: hip/femoral neck (23%), feet (23%, all women), wrist (18%), and spine (9%, all men). Nine patients (36%) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27%) and documented pyrophosphate arthropathy (14%) were only observed in women. Median minimum serum AP was 43% below the lower normal limit. Urine PEA was elevated in 15/16 patients (94%). PLP median was 68 μg/L (normal, 5-50 μg/L) and all (n = 8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia.These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP.

Original languageEnglish (US)
Pages (from-to)21-27
Number of pages7
JournalBone
Volume54
Issue number1
DOIs
StatePublished - May 2013

Fingerprint

Hypophosphatasia
Pyridoxal Phosphate
Chondrocalcinosis
Alkaline Phosphatase
Musculoskeletal Pain
Osteomalacia
Urine
Tooth Abnormalities
Rickets
Joint Diseases
Femur Neck
Hip Fractures
Diphosphonates
Genetic Testing
Wrist
Serum
Femur
Medical Records
Hip
Foot

Keywords

  • Alkaline phosphatase
  • Hypophosphatasia
  • Osteomalacia
  • Osteoporosis
  • Subtrochanteric femur fractures

ASJC Scopus subject areas

  • Physiology
  • Endocrinology, Diabetes and Metabolism
  • Histology

Cite this

Berkseth, K. E., Tebben, P., Drake, M. M., Hefferan, T. E., Jewison, D. E., & Wermers, R. A. (2013). Clinical spectrum of hypophosphatasia diagnosed in adults. Bone, 54(1), 21-27. https://doi.org/10.1016/j.bone.2013.01.024

Clinical spectrum of hypophosphatasia diagnosed in adults. / Berkseth, Kathryn E.; Tebben, Peter; Drake, Matthew M; Hefferan, Theresa E.; Jewison, Donna E.; Wermers, Robert A.

In: Bone, Vol. 54, No. 1, 05.2013, p. 21-27.

Research output: Contribution to journalArticle

Berkseth, KE, Tebben, P, Drake, MM, Hefferan, TE, Jewison, DE & Wermers, RA 2013, 'Clinical spectrum of hypophosphatasia diagnosed in adults', Bone, vol. 54, no. 1, pp. 21-27. https://doi.org/10.1016/j.bone.2013.01.024
Berkseth, Kathryn E. ; Tebben, Peter ; Drake, Matthew M ; Hefferan, Theresa E. ; Jewison, Donna E. ; Wermers, Robert A. / Clinical spectrum of hypophosphatasia diagnosed in adults. In: Bone. 2013 ; Vol. 54, No. 1. pp. 21-27.
@article{47d479c4e8f24b45818ac2d764550338,
title = "Clinical spectrum of hypophosphatasia diagnosed in adults",
abstract = "The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age ≥ 18. years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49. years; 68{\%} women). Most patients (68{\%}) were symptomatic at presentation with features including musculoskeletal pain (41{\%}) or incident fracture (18{\%}). A history of fracture was present in 54{\%}: hip/femoral neck (23{\%}), feet (23{\%}, all women), wrist (18{\%}), and spine (9{\%}, all men). Nine patients (36{\%}) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27{\%}) and documented pyrophosphate arthropathy (14{\%}) were only observed in women. Median minimum serum AP was 43{\%} below the lower normal limit. Urine PEA was elevated in 15/16 patients (94{\%}). PLP median was 68 μg/L (normal, 5-50 μg/L) and all (n = 8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia.These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP.",
keywords = "Alkaline phosphatase, Hypophosphatasia, Osteomalacia, Osteoporosis, Subtrochanteric femur fractures",
author = "Berkseth, {Kathryn E.} and Peter Tebben and Drake, {Matthew M} and Hefferan, {Theresa E.} and Jewison, {Donna E.} and Wermers, {Robert A.}",
year = "2013",
month = "5",
doi = "10.1016/j.bone.2013.01.024",
language = "English (US)",
volume = "54",
pages = "21--27",
journal = "Bone",
issn = "8756-3282",
publisher = "Elsevier Inc.",
number = "1",

}

TY - JOUR

T1 - Clinical spectrum of hypophosphatasia diagnosed in adults

AU - Berkseth, Kathryn E.

AU - Tebben, Peter

AU - Drake, Matthew M

AU - Hefferan, Theresa E.

AU - Jewison, Donna E.

AU - Wermers, Robert A.

PY - 2013/5

Y1 - 2013/5

N2 - The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age ≥ 18. years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49. years; 68% women). Most patients (68%) were symptomatic at presentation with features including musculoskeletal pain (41%) or incident fracture (18%). A history of fracture was present in 54%: hip/femoral neck (23%), feet (23%, all women), wrist (18%), and spine (9%, all men). Nine patients (36%) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27%) and documented pyrophosphate arthropathy (14%) were only observed in women. Median minimum serum AP was 43% below the lower normal limit. Urine PEA was elevated in 15/16 patients (94%). PLP median was 68 μg/L (normal, 5-50 μg/L) and all (n = 8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia.These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP.

AB - The presentation of hypophosphatasia (HPP) diagnosed in adults demonstrates a wide range of clinical manifestations, many of which are nonspecific. We sought to assess clinical characteristics of adult HPP by evaluation of Mayo Clinic Rochester adults diagnosed with HPP from 1976 through 2008. Subjects were identified by diagnostic code or medical records. Inclusion criteria were age ≥ 18. years at diagnosis; low serum alkaline phosphatase (AP) without bisphosphonate therapy; and one additional element: elevated pyridoxal 5'-phosphate (PLP) or urine phosphoethanolamine (PEA), evidence of osteomalacia, or family history. We were unable to distinguish manifesting carriers from silent unaffected carriers due to lack of a prospective standardized clinical evaluation and the absence of genetic testing. HPP was diagnosed in 22 unrelated adults (median age 49. years; 68% women). Most patients (68%) were symptomatic at presentation with features including musculoskeletal pain (41%) or incident fracture (18%). A history of fracture was present in 54%: hip/femoral neck (23%), feet (23%, all women), wrist (18%), and spine (9%, all men). Nine patients (36%) had multiple fractures while 4 (all women) had subtrochanteric femur fractures. Radiographic chondrocalcinosis (27%) and documented pyrophosphate arthropathy (14%) were only observed in women. Median minimum serum AP was 43% below the lower normal limit. Urine PEA was elevated in 15/16 patients (94%). PLP median was 68 μg/L (normal, 5-50 μg/L) and all (n = 8) were above normal. Symptomatic subjects had more fractures and chondrocalcinosis, lower median minimum AP and PLP and higher median PEA levels. Clinical features more common in fracture patients included symptoms at presentation, history of childhood rickets, dental abnormalities, lower median minimum AP and PLP, and higher median urine PEA. Four subjects had iliac crest bone biopsies, with 2/4 specimens consistent with osteomalacia.These results suggest that adult HPP demonstrates a wide spectrum of clinical manifestations including musculoskeletal pain, fractures, chondrocalcinosis and dental anomalies with some overlap in laboratory characteristics in relationship to disease severity. In addition to genetic and environmental factors, gender may influence the clinical expression of HPP.

KW - Alkaline phosphatase

KW - Hypophosphatasia

KW - Osteomalacia

KW - Osteoporosis

KW - Subtrochanteric femur fractures

UR - http://www.scopus.com/inward/record.url?scp=84873541157&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84873541157&partnerID=8YFLogxK

U2 - 10.1016/j.bone.2013.01.024

DO - 10.1016/j.bone.2013.01.024

M3 - Article

C2 - 23352924

AN - SCOPUS:84873541157

VL - 54

SP - 21

EP - 27

JO - Bone

JF - Bone

SN - 8756-3282

IS - 1

ER -