Chronic G_M1 gangliosidosis presenting as dystonia: I. Clinical and pathological features

Abstract

Clinical and pathological studies are reported from investigation of a 27-year-old man with GM1 gangliosidosis who experienced a slowly progressive dystonia that began about age 4, primarily affected the face and limbs, and eventually became almost totally incapacitating. There was only mild intellectual deterioration; myoclonus, seizures, and macular cherry-red spots were never observed. Postmortem examination revealed intraneuronal storage, localized predominantly to the basal ganglia, in which neurons contained round, multilamellated inclusions. Golgi studies revealed meganeurites arising from medium spiny neurons. Other areas of the central nervous system appeared relatively unaffected, although small basilar dilatations were observed in scattered cortical pyramidal neurons and Purkinje cell dendrites showed focal swellings. Vacuolated cells of the reticuloendothelial system were observed, including Kupffer cells and histiocytes in the spleen, marrow, and intestinal tract. Biochemical analysis revealed a generalized beta-galactosidase deficiency with specific accumulation of GM1 ganglioside in the basal ganglia.

Hemidystonia: a report of 22 patients and a review of the literature.

“…Sea-Blue histocytes may be seen on bone marrow biopsy.3334 It is possible that these two patients will eventually develop generalised dystonia, a more typical manifestation of the storage disorders. [35][36][37][38] Patient 11 presented with hemidystonia, peripheral neuropathy, and fasciculations suggesting motor neuron disease. His family history was unremarkable.…”

Neuropathology of Late Onset Gangliosidoses

“…observation]. In addition to the nervous system, cellular storage was noted in the reticu loendothelial system in the case of Goldman et al [12] and in his brother. The Kupffer cells in the liver con tained clear vacuoles containing filamentous profiles similar to those described in the infantile or late infantile cases.…”

“…Cases studied postmortem were limited to 3 but all showed similar unique distributional patterns of neu ronal storage affecting primarily basal ganglia [12,13]. The case reported by Goldman et al [12] showed less than normal brain weight but only slight cerebral cortical atrophy was noted grossly. The most striking finding on the gross examination of the brain was an atrophy of the head and body of the caudate nucleus and putamen.…”

“…Clinically this type is character ized by pyramidal and extrapyramidal signs with gait disturbance and dystonic movements (table 1) [10][11][12][13][14][15]. Cases studied postmortem were limited to 3 but all showed similar unique distributional patterns of neu ronal storage affecting primarily basal ganglia [12,13]. The case reported by Goldman et al [12] showed less than normal brain weight but only slight cerebral cortical atrophy was noted grossly.…”

Diagnosis of inherited metabolic disorders affecting the nervous system.

“…For example, it is now known that there are three genes located on three different chromosomes (1, 6,19) The term lysosome was proposed by DeDuve et al in 1955 for intracellular granules that were rich in hydrolytic enzymes.7 A lysosomal disease is associated with an abnormal enzyme that results in defective breakdown of the enzyme substrate.8 The product accumulates and eventually alters cell function. Because hydrolytic enzymes are present in many tissues, the diagnosis of the accumulated product or of the enzyme deficiency usually can be made with readily accessible tissues such as peripheral white blood cells or skin fibroblasts.9-1" Although most of these disorders produce symptoms at a young age, some mutations, as in adult onset GM1 gangliosidosis, lead to onset of symptoms later in life.…”