Update of the Original HDLS Kindred: Divergent Clinical Courses (P05.032)

Abstract

Objective: To update the original Hereditary Diffuse Leucoencephalopathy with Spheroids (HDLS) pedigree and corroborate the original report of a multisystem cerebral symptomatology with a wide spectrum of severity and a segregation pattern suggestive of dominant heredity. Background HDLS was first identified 1984 in a Swedish kindred with 17 cases. Average onset was age 36. Autopsy in four cases revealed the presence of axonal spheroids. Since then, approximately 20 reports appeared in the literature. Its molecular genetic background is unknown. Design/Methods: We performed genealogical and longitudinal observations of the original kindred. Forty members were examined, five telephone interviewed and one of the original HDLS cases was neuropathologically examined. The clinical course was documented. The cerebrospinal fluid (CSF) findings of two recently affected cases were examined, and one of those autopsied. Results: Of those examined, two developed HDLS during our survey and 38 were healthy. Those interviewed by telephone were healthy. One had symptoms suggestive of HDLS, but autopsy during our survey showed no spheroids. This patient, two relatives healthy at our examination, and one without symptoms at telephone interview had HDLS diagnoses in the 1984 report. Thus, 4 HDLS diagnoses were unconfirmed. The number of identified patients amounts to 15 among 75 individuals in four generations including two recent cases who demonstrated a subacute multisystem encephalopathy in Case 1 and an insidious course in Case 2. CSF showed signs of neurodegeneration without inflammation, and autopsy verified HDLS in Case 1. Conclusions: HDLS was underdiagnosed with unspecific psychiatric diagnoses in affected relatives. However, HDLS is a progressive encephalopathy dominated by a frontal lobe syndrome and distinguished by a multisystem (motor, parietal, extrapyramidal, visual) neurological syndrome, where the differential severity in two recent cases confirmed the existence of acute and chronic variants. Both have an ultimately fatal outcome. Its segregation pattern is strongly suggestive of dominant heredity. Disclosure: Dr. Sundal has nothing to disclose. Dr. Borjesson-Hanson has nothing to disclose. Dr. Linden has nothing to disclose. Dr. Zetterberg has nothing to disclose. Dr. Nordborg has nothing to disclose. Dr. Andersen has nothing to disclose. Dr. Roeber has nothing to disclose.