Dhananjaya Melkunte S, Thrupti S, Reddy Hamsa V, Nadig Anusha, Adarsh Kenchappa S, Jadhav Swati, Lalitha Parvathy, Nair Sandhya, Bhattacharyya Shaila, Lila Anurag, Sarathi Vijaya
Department of Endocrinology, Vydehi Institute of Medical Sciences and Research Center, Bengaluru, Karnataka, India.
Kangaroo Care Hospitals, Mysore, Karnataka, India.
Indian J Endocrinol Metab. 2025 Mar-Apr;29(2):188-194. doi: 10.4103/ijem.ijem_378_24. Epub 2025 Apr 29.
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.
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.
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 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 gene.
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.
低磷酸酯酶症（HPP）是一种罕见疾病，印度仅报道过两例经基因证实的病例。在此，我们报告五例经基因证实的印度低磷酸酯酶症患者，并描述他们的临床、生化和基因特征。
该研究纳入了在印度南部不同医疗中心接受治疗的经基因证实的低磷酸酯酶症患者。回顾了参与者的病例记录，并收集和分析了相关的表型和基因型信息。
病例1在4个月大时因生长发育不良就诊，发现持续高钙血症，为此接受了双膦酸盐治疗。后来发现碱性磷酸酶水平低。病例2在青春期出现双侧膝外翻和出牙延迟，放射学检查显示典型的舌状半透明区，碱性磷酸酶水平低。病例1和病例2的基因评估显示该基因存在复合杂合变异。病例1接受了阿法骨化醇酶治疗，生长情况有显著改善。病例3在33岁时出现多处椎体骨折，而病例4（42岁）和病例5（63岁）分别出现肌肉骨骼疼痛，诊断延迟8年和13年。病例3至病例5该基因存在杂合变异。
在印度最大的低磷酸酯酶症病例系列中，我们报告了五例低磷酸酯酶症患者，发现了两个新变异。我们的研究强调需要提高对该疾病的认识以改善早期诊断，同时也需要制定策略来减少在印度获得低磷酸酯酶症酶替代疗法方面的挑战。
