Nasu-Hakola disease
Summary
Nasu-Hakola disease is a rare autosomal recessive leukodystrophy characterized by early-onset dementia and systemic bone cysts, representing the extreme consequence of total microglial and osteoclast failure.
Microglial Relevance
Caused directly by bi-allelic loss-of-function variants in either TREM2 or TYROBP (DAP12). This represents the absolute functional extreme of microglial failure; without the TREM2/TYROBP signaling complex, myeloid cells cannot properly mature or survive, leading to catastrophic systemic failure in brain architecture and bone remodeling.
Last reviewed: June 4, 2026