The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance

Maria Luisa Brandi^{1

2}, Aliya A Khan³, Eric T Rush^{4

5}, Dalal S Ali³, Hatim Al-Alwani³, Khulod Almonaei³, Farah Alsarraf³, Severine Bacrot⁶, Kathryn M Dahir⁷, Karel Dandurand⁸, Chad Deal⁹, Serge Livio Ferrari¹⁰, Francesca Giusti¹¹, Gordon Guyatt¹², Erin Hatcher¹³, Steven W Ing¹⁴, Muhammad Kassim Javaid¹⁵, Sarah Khan¹⁶, Roland Kocijan¹⁷, E Michael Lewiecki¹⁸, Agnes Linglart¹⁹, Iman M'Hiri¹⁶, Francesca Marini²⁰, Mark E Nunes²¹, Cheryl Rockman-Greenberg²², Lothar Seefried²³, Jill H Simmons⁷, Susan R Starling⁴, Leanne M Ward²⁴, Liang Yao¹², Romina Brignardello-Petersen¹², Christian Roux^{25

26}

Affiliations

¹ F.I.R.M.O. Italian Foundation for the Research On Bone Diseases, Florence, Italy. marialuisa.brandi@unifi.it.
² Donatello Bone Clinic, Villa Donatello Hospital, Florence, Italy. marialuisa.brandi@unifi.it.
³ Division of Endocrinology and Metabolism, McMaster University, Hamilton, Canada.
⁴ Division of Clinical Genetics, Children's Mercy Kansas City and Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
⁵ Division of Endocrinology, Metabolism, Osteoporosis, and Genetics, Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
⁶ Department of Genetics, Centre Hospitalier de Versailles, Hôpital André Mignot, Versailles, France.
⁷ Division of Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Medicine, Endocrinology and Metabolism, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁹ Center for Osteoporosis and Metabolic Bone Disease, Department of Rheumatology, The Cleveland Clinic Foundation, Cleveland, OH, USA.
¹⁰ Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹¹ Donatello Bone Clinic, Villa Donatello Hospital, Florence, Italy.
¹² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹³ Neuromuscular Clinic, McMaster University Medical Centre, Hamilton Health Sciences, Hamilton, ON, Canada.
¹⁴ Division of Endocrinology, Diabetes, & Metabolism, Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁵ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
¹⁶ Bone Research and Education Centre, Oakville, ON, Canada.
¹⁷ Trauma Centre Meidling, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA, 1St Medical Department Hanusch Hospital, 1140, Vienna, Austria.
¹⁸ New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.
¹⁹ APHP, Bicêtre Paris-Sud, University Paris Sud, Paris-Saclay, Le Kremlin Bicêtre, Paris, France.
²⁰ F.I.R.M.O. Italian Foundation for the Research On Bone Diseases, Florence, Italy.
²¹ Division of Medical Genetics and Metabolism, Valley Children's HealthCare, Madera, CA, USA.
²² Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
²³ Musculoskeletal Center Würzburg, University of Würzburg, Würzburg, Germany.
²⁴ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
²⁵ INSERM CRESS UMR 1153, Paris, France.
²⁶ Université Paris-Cité, Department of Rheumatology, APHP-Centre, Cochin Hospital, Paris, France.

PMID: 37982856
DOI: 10.1007/s00198-023-06859-8

Review

The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance

Maria Luisa Brandi et al. Osteoporos Int. 2024 Mar.

. 2024 Mar;35(3):439-449.

doi: 10.1007/s00198-023-06859-8. Epub 2023 Nov 20.

Authors

Affiliations

¹ F.I.R.M.O. Italian Foundation for the Research On Bone Diseases, Florence, Italy. marialuisa.brandi@unifi.it.
² Donatello Bone Clinic, Villa Donatello Hospital, Florence, Italy. marialuisa.brandi@unifi.it.
³ Division of Endocrinology and Metabolism, McMaster University, Hamilton, Canada.
⁴ Division of Clinical Genetics, Children's Mercy Kansas City and Department of Pediatrics, University of Missouri-Kansas City School of Medicine, Kansas City, MO, USA.
⁵ Division of Endocrinology, Metabolism, Osteoporosis, and Genetics, Department of Internal Medicine, University of Kansas School of Medicine, Kansas City, KS, USA.
⁶ Department of Genetics, Centre Hospitalier de Versailles, Hôpital André Mignot, Versailles, France.
⁷ Division of Endocrinology and Metabolism, Vanderbilt University Medical Center, Nashville, TN, USA.
⁸ Department of Medicine, Endocrinology and Metabolism, Université de Sherbrooke, Sherbrooke, QC, Canada.
⁹ Center for Osteoporosis and Metabolic Bone Disease, Department of Rheumatology, The Cleveland Clinic Foundation, Cleveland, OH, USA.
¹⁰ Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospitals and Faculty of Medicine, Geneva, Switzerland.
¹¹ Donatello Bone Clinic, Villa Donatello Hospital, Florence, Italy.
¹² Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
¹³ Neuromuscular Clinic, McMaster University Medical Centre, Hamilton Health Sciences, Hamilton, ON, Canada.
¹⁴ Division of Endocrinology, Diabetes, & Metabolism, Ohio State University Wexner Medical Center, Columbus, OH, USA.
¹⁵ Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK.
¹⁶ Bone Research and Education Centre, Oakville, ON, Canada.
¹⁷ Trauma Centre Meidling, Ludwig Boltzmann Institute of Osteology at Hanusch Hospital of OEGK and AUVA, 1St Medical Department Hanusch Hospital, 1140, Vienna, Austria.
¹⁸ New Mexico Clinical Research & Osteoporosis Center, Albuquerque, NM, USA.
¹⁹ APHP, Bicêtre Paris-Sud, University Paris Sud, Paris-Saclay, Le Kremlin Bicêtre, Paris, France.
²⁰ F.I.R.M.O. Italian Foundation for the Research On Bone Diseases, Florence, Italy.
²¹ Division of Medical Genetics and Metabolism, Valley Children's HealthCare, Madera, CA, USA.
²² Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.
²³ Musculoskeletal Center Würzburg, University of Würzburg, Würzburg, Germany.
²⁴ Department of Pediatrics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada.
²⁵ INSERM CRESS UMR 1153, Paris, France.
²⁶ Université Paris-Cité, Department of Rheumatology, APHP-Centre, Cochin Hospital, Paris, France.

PMID: 37982856
DOI: 10.1007/s00198-023-06859-8

Erratum in

Correction: Hypophosphatasia diagnosis: current state of the art and proposed diagnostic criteria for children and adults.
Khan AA, Brandi ML, Rush ET, Ali DS, Al-Alwani H, Almonaei K, Alsarraf F, Bacrot S, Dahir KM, Dandurand K, Deal C, Ferrari SL, Giusti F, Guyatt G, Hatcher E, Ing SW, Javaid MK, Khan S, Kocijan R, Linglart A, M'Hiri I, Marini F, Nunes ME, Rockman-Greenberg C, Roux C, Seefried L, Simmons JH, Starling SR, Ward LM, Yao L, Brignardello-Petersen R, Michael Lewiecki E. Khan AA, et al. Osteoporos Int. 2024 May;35(5):933-934. doi: 10.1007/s00198-024-07048-x. Osteoporos Int. 2024. PMID: 38498158 Free PMC article. No abstract available.

Abstract

Hypophosphatasia (HPP) is an inborn error of metabolism caused by reduced or absent activity of the tissue non-specific alkaline phosphatase (TNSALP) enzyme, resulting from pathogenic variants in the ALPL gene. Clinical presentation of HPP is highly variable, including lethal and severe forms in neonates and infants, a benign perinatal form, mild forms manifesting in adulthood, and odonto-HPP. Diagnosis of HPP remains a challenge in adults, as signs and symptoms may be mild and non-specific. Disease presentation varies widely; there are no universal signs or symptoms, and the disease often remains underdiagnosed or misdiagnosed, particularly by clinicians who are not familiar with this rare disorder. The absence of diagnosis or a delayed diagnosis may prevent optimal management for patients with this condition. Formal guidelines for the diagnosis of adults with HPP do not exist, complicating efforts for consistent diagnosis. To address this issue, the HPP International Working Group selected 119 papers that explicitly address the diagnosis of HPP in adults through a Medline, Medline In-Process, and Embase search for the terms "hypophosphatasia" and "HPP," and evaluated the pooled prevalence of 17 diagnostic characteristics, initially selected by a group of HPP clinical experts, in eligible studies and in patients included in these studies. Six diagnostic findings showed a pooled prevalence value over 50% and were considered for inclusion as major diagnostic criteria. Based on these results and according to discussion and consideration among members of the Working Group, we finally defined four major diagnostic criteria and five minor diagnostic criteria for HPP in adults. Authors suggested the integrated use of the identified major and minor diagnostic criteria, which either includes two major criteria, or one major criterion and two minor criteria, for the diagnosis of HPP in adults.

Keywords: Diagnostic parameters; HPP diagnosis in adults; Hypophosphatasia; Systematic review.

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References

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The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance

Affiliations

The challenge of hypophosphatasia diagnosis in adults: results from the HPP International Working Group Literature Surveillance

Authors

Affiliations

Erratum in

Abstract

References

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