Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia

Introduction: Hypophosphatasia (HPP) is a rare disorder, with only two genetically proven cases reported from India. Here, We report five Indian patients with genetically proven hypophosphatasia and describe their clinical, biochemical, and genetic profiles. Methods: The study included patients with...

Full description

Saved in:
Bibliographic Details
Main Authors: Melkunte S. Dhananjaya, S. Thrupti, Hamsa V. Reddy, Anusha Nadig, Kenchappa S. Adarsh, Swati Jadhav, Parvathy Lalitha, Sandhya Nair, Shaila Bhattacharyya, Anurag Lila, Vijaya Sarathi
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2025-03-01
Series:Indian Journal of Endocrinology and Metabolism
Subjects:
Online Access:https://journals.lww.com/10.4103/ijem.ijem_378_24
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849324206994489344
author Melkunte S. Dhananjaya
S. Thrupti
Hamsa V. Reddy
Anusha Nadig
Kenchappa S. Adarsh
Swati Jadhav
Parvathy Lalitha
Sandhya Nair
Shaila Bhattacharyya
Anurag Lila
Vijaya Sarathi
author_facet Melkunte S. Dhananjaya
S. Thrupti
Hamsa V. Reddy
Anusha Nadig
Kenchappa S. Adarsh
Swati Jadhav
Parvathy Lalitha
Sandhya Nair
Shaila Bhattacharyya
Anurag Lila
Vijaya Sarathi
author_sort Melkunte S. Dhananjaya
collection DOAJ
description Introduction: Hypophosphatasia (HPP) is a rare disorder, with only two genetically proven cases reported from India. Here, We report five Indian patients with genetically proven hypophosphatasia and describe their clinical, biochemical, and genetic profiles. Methods: The study included patients with genetically proven hypophosphatasia managed at different healthcare centers in South India. The participants’ case records were reviewed, and relevant phenotypic and genotypic information was collected and analyzed. Results: Case 1 presented at 4 months of age for failure to thrive, found to have persistent hypercalcemia for which she received bisphosphonate therapy. A low alkaline phosphatase was recognized later. Case 2 presented during adolescence with bilateral genu valgus and delayed dentition with classical tongue-like translucencies on radiology and low alkaline phosphatase. Genetic evaluation in cases 1 and 2 revealed compound heterozygous variants in the ALPL gene. Case 1 received asfotase alfa with remarkable improvement in growth. Case 3 presented with multiple vertebral fractures at 33 years of age whereas cases 4 (42 years) and 5 (63 years) presented with musculoskeletal pains with delayed diagnosis for 8 and 13 years, respectively. Cases 3–5 had heterozygous variants in the ALPL gene. Conclusions: In the largest case series of hypophosphatasia from India, we report five cases of hypophosphatasia with two novel variants. Our study emphasizes the need to increase awareness regarding the disease to improve its early diagnosis and also, the need to form strategies to reduce the challenges in obtaining enzyme replacement therapy for hypophosphatasia in India.
format Article
id doaj-art-8f9d9b8cb73f429b86edfd6c4d21c3b4
institution Kabale University
issn 2230-8210
2230-9500
language English
publishDate 2025-03-01
publisher Wolters Kluwer Medknow Publications
record_format Article
series Indian Journal of Endocrinology and Metabolism
spelling doaj-art-8f9d9b8cb73f429b86edfd6c4d21c3b42025-08-20T03:48:46ZengWolters Kluwer Medknow PublicationsIndian Journal of Endocrinology and Metabolism2230-82102230-95002025-03-0129218819410.4103/ijem.ijem_378_24Phenotypic and Genotypic Spectrum of Indian Patients with HypophosphatasiaMelkunte S. DhananjayaS. ThruptiHamsa V. ReddyAnusha NadigKenchappa S. AdarshSwati JadhavParvathy LalithaSandhya NairShaila BhattacharyyaAnurag LilaVijaya SarathiIntroduction: Hypophosphatasia (HPP) is a rare disorder, with only two genetically proven cases reported from India. Here, We report five Indian patients with genetically proven hypophosphatasia and describe their clinical, biochemical, and genetic profiles. Methods: The study included patients with genetically proven hypophosphatasia managed at different healthcare centers in South India. The participants’ case records were reviewed, and relevant phenotypic and genotypic information was collected and analyzed. Results: Case 1 presented at 4 months of age for failure to thrive, found to have persistent hypercalcemia for which she received bisphosphonate therapy. A low alkaline phosphatase was recognized later. Case 2 presented during adolescence with bilateral genu valgus and delayed dentition with classical tongue-like translucencies on radiology and low alkaline phosphatase. Genetic evaluation in cases 1 and 2 revealed compound heterozygous variants in the ALPL gene. Case 1 received asfotase alfa with remarkable improvement in growth. Case 3 presented with multiple vertebral fractures at 33 years of age whereas cases 4 (42 years) and 5 (63 years) presented with musculoskeletal pains with delayed diagnosis for 8 and 13 years, respectively. Cases 3–5 had heterozygous variants in the ALPL gene. Conclusions: In the largest case series of hypophosphatasia from India, we report five cases of hypophosphatasia with two novel variants. Our study emphasizes the need to increase awareness regarding the disease to improve its early diagnosis and also, the need to form strategies to reduce the challenges in obtaining enzyme replacement therapy for hypophosphatasia in India.https://journals.lww.com/10.4103/ijem.ijem_378_24alpl genehypophosphatasiaindia
spellingShingle Melkunte S. Dhananjaya
S. Thrupti
Hamsa V. Reddy
Anusha Nadig
Kenchappa S. Adarsh
Swati Jadhav
Parvathy Lalitha
Sandhya Nair
Shaila Bhattacharyya
Anurag Lila
Vijaya Sarathi
Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia
Indian Journal of Endocrinology and Metabolism
alpl gene
hypophosphatasia
india
title Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia
title_full Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia
title_fullStr Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia
title_full_unstemmed Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia
title_short Phenotypic and Genotypic Spectrum of Indian Patients with Hypophosphatasia
title_sort phenotypic and genotypic spectrum of indian patients with hypophosphatasia
topic alpl gene
hypophosphatasia
india
url https://journals.lww.com/10.4103/ijem.ijem_378_24
work_keys_str_mv AT melkuntesdhananjaya phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT sthrupti phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT hamsavreddy phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT anushanadig phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT kenchappasadarsh phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT swatijadhav phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT parvathylalitha phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT sandhyanair phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT shailabhattacharyya phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT anuraglila phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia
AT vijayasarathi phenotypicandgenotypicspectrumofindianpatientswithhypophosphatasia