Neurol Clin 1989 Feb;7(1):75-88

Niemann-Pick disease types C and D

Brady RO, Filling-Katz MR, Barton NW, Pentchev PG
Developmental and Metabolic Neurology Branch, National Institute of Neurological
and Communicative Disorders and Stroke, Bethesda, Maryland.

Abstract
Patients grouped into categories termed type C Niemann-Pick disease and the Nova
Scotia isolate called type D Niemann-Pick disease are characterized by mild to
moderate hepatosplenomegaly, sea-blue histiocytes in the bone marrow,
supranuclear gaze paresis in the vertical plane, slowly progressing ataxia, and
mental deterioration. These signs are caused by abnormal intracellular
cholesterol homeostasis. Cholesterol that enters cells from the circulation
through the LDL receptor is not processed in a timely, normal manner by cells in
parenchymal organs and the CNS. It therefore accumulates in toxic quantities as
unesterified cholesterol causing cellular and tissue damage. Knowledge of the
primary, consistent disturbance in cholesterol disposition has led to the
development of tests to diagnose patients, identify heterozygotes, and assure
the prenatal detection of these disorders. Therapeutic strategies include
reduction of dietary cholesterol, apheresis techniques designed to reduce LDL
cholesterol available to cells, and reduction of formation of LDL and increase
of synthesis of HDL to lower cellular uptake of cholesterol and enhance egress
of this lipid from intracellular storage sites. The development of procedures
that block cholesterol formation but do not up-regulate LDL receptors on plasma
cell membranes is considered to be highly important for the therapy of types C
and D Niemann-Pick disease