Objective: To describe a case of CASR mutation-related hypocalcemia presenting with progressive movement disorder, cognitive decline, and widespread brain calcifications, illustrating the overlap between metabolic and neurodegenerative disorders.

Background: Autosomal Dominant Hypocalcemia (ADH1) is caused by mutations in the calcium-sensing receptor (CASR), leading to chronic hypocalcemia, and hypercalciuria. While primarily an endocrine disorder, intracranial calcifications contribute to movement disorders, cognitive dysfunction, and speech abnormalities.

The mechanism of brain calcification in ADH1 remains incompletely understood. Studies suggest hyperphosphatemia may contribute, mirroring primary familial brain calcification (PFBC). This case highlights diagnostic challenges, particularly in distinguishing ADH1 from PFBC and atypical parkinsonism.

Method: We present a 52-year-old man with a CASR mutation and longstanding hypocalcemia, who developed progressive extra-pyramidal symptoms, gait dysfunction, and cognitive impairment.

Examination revealed:

• Limb bradykinesia, cogwheel rigidity, and dysdiadochokinesia.

• Mild ataxia, without dystonia.

• Oculomotor dysfunction.

• Mild cognitive impairment (MoCA: 22/30), with hypophonia, logopenia, and the head-turn sign, suggestive of early dementia.

CT head showed:

• Extensive bilateral basal ganglia, thalamic, and occipital calcifications.

Results: • We found a mild response to L-dopa, with improved movement initiation and execution.

• Better calcium management with weekly blood monitoring appeared to slow disease progression.

• No new treatments trialed, though CASR-targeting therapies such as Encaleret are under investigation.

Conclusion: This case underscores the neurological phenotype of CASR mutations and the association between brain calcifications and parkinsonism. While ADH1 is typically managed as a calcium homeostasis disorder, its neurological impact remains underrecognized. The exact mechanism of calcification in ADH1 remains unclear, but hyperphosphatemia and phosphate-mediated mineral deposition are likely contributors.

Clinical recognition is crucial, as these patients are often misdiagnosed with atypical parkinsonism, thyroid disorders, or PFBC. Earlier identification of ADH1 could allow for better calcium management, potentially preventing or mitigating irreversible neurological damage.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/a-case-of-autosomal-dominant-hypocalcemia-presenting-with-parkinsonism-and-widespread-brain-calcifications/