title: Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS): a misdiagnosed disease entity.
abstract: Hereditary diffuse leukoencephalopathy with spheroids (HDLS) was originally described in a large Swedish pedigree. Since then, 22 reports describing a total of 13 kindreds and 11 sporadic cases have been published. Inheritance is autosomal dominant, albeit the gene is unknown. Here we report on the clinical findings, genealogical data, brain MRI data, and autopsy/biopsy findings of four probands from three independently ascertained novel families from Norway, Germany and US. We identified a 39-year-old female and her twin sister, a 52-year-old male and a 47-year-old male with progressive neurological illness characterized by personality changes, cognitive decline and motor impairments, such as gait problems, bradykinesia, tremor and rigidity. Brain MRI showed white matter abnormalities with frontal prominence. Brain biopsy/autopsies were consistent with HDLS. HDLS is an under-recognized disease and in reporting these cases, we aim to increase the awareness of the disorder. Due to varied and wide phenotypic presentations, which may imitate several neurodegenerative diseases, HDLS can be difficult to diagnose. Definitive diagnosis can be established only by direct brain tissue examination. Familiarity with the clinical presentation and typical neuroimaging findings may be helpful in narrowing the diagnosis.
authors: Department of Neurology, Mayo Clinic, Jacksonville, FL 32224, USA.
authors: Christina
authors: C
authors: Sundal
authors: Jennifer
authors: J
authors: Lash
authors: Jan
authors: J
authors: Aasly
authors: Sarka
authors: S
authors: Øygarden
authors: Sigrun
authors: S
authors: Roeber
authors: Hans
authors: H
authors: Kretzschman
authors: James Y
authors: JY
authors: Garbern
authors: Alex
authors: A
authors: Tselis
authors: Rosa
authors: R
authors: Rademakers
authors: Dennis W
authors: DW
authors: Dickson
authors: Daniel
authors: D
authors: Broderick
authors: Zbigniew K
authors: ZK
authors: Wszolek
mesh_terms: D000328:Adult; D001344:Autopsy; D001369:Axons / Q000473:pathology*; D001706:Biopsy; D001921:Brain / Q000473:pathology; D003072:Cognition Disorders / Q000209:etiology; D003937:Diagnosis, Differential; D003951:Diagnostic Errors; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D056784:Leukoencephalopathies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D001523:Mental Disorders / Q000209:etiology; D009069:Movement Disorders / Q000209:etiology; D059906:Neuroimaging; D012189:Retrospective Studies; D018874:Spheroids, Cellular / Q000473:pathology*