Biallelic SLC20A2 loss-of-function in severe early-onset neurodevelopmental disorder with brain calcification.
Mehmet Burak Mutlu, Abdullah Sezer, Elif Özdemir et al.
✦ AI-curated · Sources linked
Case in brief
A child presented in early infancy with refractory seizures, severe hypotonia, left hemiplegia, profound developmental impairment, bilateral cataracts, and progressive intracranial calcification. Imaging showed vascular and leptomeningeal calcification, arterial narrowing, cytotoxic edema, subdural effusion, and rapid cerebral atrophy. Sequencing identified a homozygous SLC20A2 nonsense variant, c.1652 G > A, p.(Trp551Ter); both heterozygous parents had radiologic findings consistent with SLC20A2-related primary brain calcification. Patient fibroblasts showed markedly reduced SLC20A2 expression, supporting biallelic loss of function.
What made this case unusual
The severe early-onset presentation combined prominent vascular and leptomeningeal calcification with arterial narrowing, cytotoxic edema, subdural effusion, and rapid cerebral atrophy.
Diagnostic / clinical pearl
In a child with severe neurodevelopmental disease and progressive brain calcification, consider biallelic SLC20A2 loss of function; the associated imaging may include vascular and leptomeningeal calcification.
Why it matters
The case supports a dose-dependent SLC20A2 disease spectrum, with biallelic loss of function associated with severe childhood-onset disease distinct from classical adult-onset primary brain calcification.