Hereditary diffuse leukoencephalopathy with spheroids is a rare autosomal dominant disorder characterized by cerebral white matter degeneration with axonal spheroids leading to progressive cognitive and motor dysfunction.

Pathology

There is enlargement of the lateral ventricles and marked attenuation of cerebral white matter.[1] The loss of white matter is caused by myelin loss. These changes are associated with diffuse gliosis, moderate loss of axons and many axonal spheroids. Spheroids had thin or discontinuous or no myelin sheaths. Macrophages with non-metachromatic lipid granules are common.

Genetics

The cause of this disease appears to be due to mutations in the colony stimulating factor 1 receptor.[2] The mutations are concentrated in tyrosine kinase domain of the protein.

Clinically

The presentation may be variable with forgetfulness, global intellectual deterioration with amnesia, spatiotemporal disorientation and impairment of judgement.

References

  1. ^ Baba Y, Ghetti B, Baker MC, Uitti RJ, Hutton ML, Yamaguchi K, Bird T, Lin W, DeLucia MW, Dickson DW, Wszolek ZK (2006) Hereditary diffuse leukoencephalopathy with spheroids: clinical, pathologic and genetic studies of a new kindred. Acta Neuropathol 111(4):300-311
  2. ^ Rademakers R, Baker M, Nicholson AM, Rutherford NJ, Finch N, Soto-Ortolaza A, Lash J, Wider C, Wojtas A, Dejesus-Hernandez M, Adamson J, Kouri N, Sundal C, Shuster EA, Aasly J, Mackenzie J, Roeber S, Kretzschmar HA, Boeve BF, Knopman DS, Petersen RC, Cairns NJ, Ghetti B, Spina S, Garbern J, Tselis AC, Uitti R, Das P, Van Gerpen JA, Meschia JF, Levy S, Broderick DF, Graff-Radford N, Ross OA, Miller BB, Swerdlow RH, Dickson DW, Wszolek ZK (2011) Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids. Nat Genet doi: 10.1038/ng.1027.
More