POLD and HDLS diseases form a single disease entity

Written on Thursday 12 June 2014

Pigmented orthochromatic leukodystrophy (or POLD) and hereditary diffuse leukoencephalopathy with axonal spheroids (or HDLS) are rare neurodegenerative diseases characterised by abnormalities of the brain white matter, a loss of myelin and a swelling of axons.

Although considered as two distinct illnesses, their pathological and clinical characteristics suggest the opposite. However, no genetic or mechanistic link between these two diseases has been reported to date.
Recently, mutations in the CSF1R gene have been identified in families suffering from HDLS. The objective of this study is to determine if CSF1R mutations are responsible for POLD. Therefore, CSF1R sequencing was performed in two POLD families and CSF1R mutations were identified. Histological studies in POLD patients showed typical neurological injury of HDLS.
Thus, the first genetic evidence provided by this study show HDLS and POLD represent a single clinical entity. A new name for this clinical entity is proposed: ALSP for « Adult-onset Leukoencephalopathy with axonal Spheroids and Pigmented glia »

Illnesses: Pigmented orthochromatic leukodystrophy (POLD) and hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS)
Subjects: Two families affected by POLD
Study type: Genetic
Laboratory: Dr. Rosa Rademakers, Department of Neuroscience, Mayo Clinic, Jacksonville, FL, USA.

Source : A.M. Nicholson, M.C. Baker, N.A. Finch, N.J. Rutherford, C. Wider, N.R. Graff-Radford, P.T. Nelson, H.B. Clark, Z.K. Wszolek, D.W. Dickson, D.S. Knopman, R. Rademakers. CSF1R mutations link POLD and HDLS as a single disease entity. Neurology 2013, 80(11):1033-40.

Scientific information provided in collaboration with the INIST-CNRS Institute, Institute for Scientific and Technical Information