Neuropathology of the Norrbottnian type of Gaucher disease. Morphological and biochemical studies.

The Norrbottnian type of Gaucher disease is characterized by infantile or juvenile onset and variable degrees of neurological symptoms, some of which develop only after splenectomy. A full neuropathological description of this type of Gaucher disease has not been reported previously. The brains of five patients were examined morphologically and biochemically. All presented typical accumulations of glucosylceramide storing cells in the adventitia of vessels in the cerebral and cerebellar sub-cortical white matter (s.c.w.m.). There were differences between the five cases with regard to the accumulation of adventitial storage cells and to the fatty acid pattern of the glucosylceramide isolated from the s.c.w.m., which implicate that the accumulation of glucosylceramide in adventitial cells in the brain is dependent on the generalized lipid storage process and enhanced by splenectomy. Loss of neurones and myelin was noted in the vicinity of accumulations of storage cells in two cases. The five cases showed varying degrees of nerve cell loss, satellitosis and neuronophagia. Lipofuscin with simple and complex lipids but no glycolipids could be demonstrated in neurones light-microscopically. Ultrastructural examination revealed inclusion bodies with bilayers in neurones of the cerebral and cerebellar cortex, dentate nucleus and pons. Because of the bilayered structure of Gaucher cell inclusions the bilayers in neurones are assumed to be formed by glucosylceramide. The fatty acid composition of glucosylceramide isolated from cerebral cortex in all cases suggested that cerebral gangliosides were its main precursor. The highest levels of psychosine (glucosylsphingosine) were seen in the cases with the most advanced nerve cell loss. The morphological and biochemical findings indicate that the neuronopathic process is associated with accumulation of glucosylceramide and psychosine in neurones.