Renal and Systemic Complications in Autosomal Dominant Hypocalcaemia Type 1: A Case Series from North East England

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Abstract Context Autosomal dominant hypocalcaemia type 1 (ADH1) is a rare genetic disorder caused by activating CASR variants, characterised by hypocalcaemia, low/normal parathyroid hormone, and hypercalciuria. While managed with conservative calcium targets to prevent renal damage, the long-term systemic burden remains poorly defined. Design This descriptive case series reviewed nine adults with genetically confirmed ADH1 in North East England (2005–2024). Clinical, biochemical, and imaging data were retrospectively analysed from electronic records. Pathogenic CASR variants were identified via accredited genomic panels. Results The cohort (n=9; 5 female; age 24–57) was 89% familial, with all exhibiting persistent hypocalcaemia and 66% presenting with hypomagnesaemia. Renal involvement affected 78%, including nephrocalcinosis (56%), nephrolithiasis (67%), and chronic kidney disease, with two patients from one kindred progressing to kidney failure and death. Extra-renal features included seizures, intracranial calcifications, dental abnormalities, and neuropsychiatric symptoms, often persisting despite conservative strategies to limit calcium supplementation post-diagnosis. No clear correlation was found between mean serum calcium levels and disease severity, highlighting significant phenotypic variability. Conclusions ADH1 is a multisystem disorder with substantial morbidity, including nephrocalcinosis, chronic kidney disease and a risk of kidney failure despite cautious management. Other significant features include hypocalcaemic seizures and intracranial calcification. These findings emphasise the necessity of early genetic diagnosis, family screening, and longitudinal renal surveillance. The high complication burden under conventional therapy underscores the need for targeted treatments, such as CaSR antagonists (calcilytics), to improve long-term outcomes.

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