Nasu-Hakola disease due to a homozygous triggering receptor expressed on myeloid cell 2 gene mutation / 中华神经科杂志

ABSTRACT

Nasu-Hakola disease is an extremely rare genetic disorder with cognitive dysfunction and fractures as the main clinical manifestations. The clinical characteristics, laboratory, imaging, and genetic data of a Nasu-Hakola case from a consanguineous Chinese family were analyzed. The patient was a 40-year-old female complaining about progressive forgetting and behavior change of three years and urinary incontinence of eight months. Neurological examination of the patient showed tetra-pyramidal signs. Neuropsychological testing revealed severe cognitive and behavioral impairment. Head magnetic resonance imaging showed generalized brain atrophy predominantly involving the frontal lobe, caudate nucleus, and anterior corpus callosum, and head computer tomography showed bilateral basal ganglia calcification. The patient had no history of bone pain or fracture and a skeletal survey showed no abnormalities. Whole exome sequencing identified a novel homozygous triggering receptor expressed on myeloid cells 2 gene mutation (c.523delA) in the patient and confirmed the heterozygous status of her parents and sisters. The patient showed no signs of improvement during the last six months after discharge. Although the patient′s clinical presentations mimicked the behavioral variant of frontotemporal dementia, reduced 42-amino acid form of amyloid-β protein level in the cerebrospinal fluid suggested amyloid deposition in the brain, which might be related to astrocytic dysfunction.