A clinical, genetic, and treatment analysis of two Vietnamese patients with vitamin D-dependent rickets type 1A
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https://doi.org/10.15625/vjbt-23261Keywords:
25-hydroxyvitamin D-1α-hydroxylase deficiency, autosomal recessive inheritance, calcitriol treatment, CYP27B1, vitamin D-dependent rickets type 1A.Abstract
This study examined the clinical and genetic features of two unrelated Vietnamese families exhibiting the characteristic symptoms of vitamin D-dependent rickets type 1A (VDDR-1A). The affected patients presented with prominent skeletal deformities, severe hypocalcemia, and markedly elevated serum levels of alkaline phosphatase (ALP) and parathyroid hormone (PTH), despite having normal or elevated concentrations of 25-hydroxyvitamin D [25(OH)D]. Genetic analysis revealed a homozygous frameshift mutation (c.1319_1325dupCCCACCC; p.Phe443Profs*24) in both patients. This previously reported pathogenic variant follows an autosomal recessive inheritance pattern. In both families, the asymptomatic parents were confirmed to be heterozygous carriers, and the patients’ siblings carried the mutation in a heterozygous state but exhibited no clinical manifestations. This mutation appears to result in early-onset and severe skeletal abnormalities, consistent with the phenotype observed in our patients. Treatment with calcitriol led to significant clinical and biochemical improvement over time, including normalization of calcium and PTH levels and a reduction in skeletal symptoms. Continued follow-up has demonstrated sustained improvement, highlighting the efficacy of targeted therapy in genetically confirmed cases. Our findings underscore the importance of incorporating genetic testing into the diagnostic pathway for children presenting with unexplained rickets-like symptoms. Early identification of causative mutations facilitates timely intervention, the development of optimized treatment strategies, and the prevention of long-term complications. Moreover, molecular diagnosis provides a basis for targeted genetic counselling, enabling families to better understand the condition and its implications. This approach supports the assessment of recurrence risk, identification of asymptomatic carriers among relatives, and informed reproductive decision-making. As such, genetic screening plays a pivotal role not only in individual patient management but also in shaping broader public health strategies, particularly in populations where inherited disorders may be underrecognized or underdiagnosed.
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