RESUMEN
Hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and familial pigmentary orthochromatic leukodystrophy (POLD) present as adult-onset dementia with motor impairment and epilepsy. They are regarded as distinct diseases. We review data from the literature that support their being a single entity. Apart from a slightly older age at onset, a more rapid course, and more prominent pyramidal tract involvement, familial POLD is clinically similar to HDLS. Moreover, the pathologic hallmarks of the two diseases, axonal spheroids in HDLS and pigmented macrophages in POLD, can be identified in both conditions. This supports HDLS and POLD being referred collectively as adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP).
Asunto(s)
Axones/patología , Demencia Vascular/patología , Demencia/patología , Leucodistrofia Metacromática/patología , Degeneración Walleriana/patología , Edad de Inicio , Demencia/fisiopatología , Demencia Vascular/fisiopatología , Progresión de la Enfermedad , Humanos , Leucodistrofia Metacromática/fisiopatología , Macrófagos/patología , Neuroglía/patología , Degeneración Walleriana/fisiopatologíaRESUMEN
OBJECTIVE: To report a new American family with hereditary diffuse leukoencephalopathy with spheroids (HDLS), including serial, presymptomatic and symptomatic, cranial MRIs from the proband. METHODS: We report clinical and genealogic investigations of an HDLS family, sequential brain MRIs of the proband, and autopsy slides of brain tissue from the proband's father. RESULTS: We identified seven affected family members (five deceased). The mean age at symptomatic disease onset was 35 years (range: 20-57), and the mean disease duration was 16 years (range: 3-46). Five affected individuals initially manifested memory disturbance and behavioral changes, whereas two experienced a mood disorder as their presenting symptom. Our proband's father had been diagnosed clinically with vascular dementia, but his brain autopsy was consistent with HDLS. The proband had a cranial MRI prior to symptom onset, with two subsequent MRIs performed during follow-up. These serial images reveal a progressive, confluent, frontal-predominant leukoencephalopathy with symmetric cortical atrophy. CONCLUSIONS: The proband of our newly identified hereditary diffuse leukoencephalopathy with spheroids (HDLS) kindred had subtle evidence of an incipient leukoencephalopathy on a presymptomatic cranial MRI. Conceivably, MRI may facilitate identifying affected presymptomatic individuals within known HDLS kindreds, increasing the likelihood of isolating the causative genes.