Abnormalities of developing white matter in lysosomal storage diseases

Area of Science:

• Neuroscience
• Biochemistry
• Pathology

Background:

• Lysosomal storage diseases (LSDs) are inborn errors of metabolism affecting cellular function.
• Neuroradiologic studies suggest delayed central nervous system (CNS) myelination in infantile LSDs.
• This contrasts with the primary neuronal focus of many LSDs.

Purpose of the Study:

• To review neuropathologic findings in the CNS white matter of patients and animal models with LSDs.
• To correlate neuropathology with normal myelinogenesis.
• To propose mechanisms for white matter deficiency in LSDs.

Main Methods:

• Review of published neuropathologic evaluations of infantile and juvenile LSD patients.
• Examination of corresponding animal models of LSDs.
• Analysis of studies on normal myelinogenesis biochemistry and anatomy.

Main Results:

• Neuropathologic evidence indicates central white matter involvement in infantile and juvenile LSDs.
• Observed white matter pathology is consistent with impaired myelinogenesis.
• Animal models corroborate findings in human patients.

Conclusions:

• Delayed myelination in LSDs may stem from direct metabolic effects on oligodendrocytes.
• Oligodendrocyte dysfunction impacts myelin formation and maintenance.
• Secondary axonal and neuronal damage also contribute to white matter deficits in LSDs.