This is probably an autosomal recessive disease without ethnic predominance. The infants appear abnormal at birth. They have dysmorphic facial features, like those of the mucopolysaccharidoses: depressed and wide nasal bridge, frontal bossing, hypertelorism, puffy eyelids, long upper lip, gingival and alveolar hypertrophy, macroglossia, and low-set ears. These features, with the bone changes mentioned below, account for the term pseudo-Hurler. Other indications of the disease are the onset of impaired awareness and reduced responsivity in the first days or weeks of life; lack of psychomotor development after 3 to 6 months; hypotonia, and later hypertonia with lively tendon reflexes and Babinski signs. Seizures are frequent. The head size is variable (microcephaly more often than macrocephaly). Loss of vision, coarse nystagmus and strabismus, macular cherry-red spots (in half the cases), flexion pseudocontractures of elbows and knees, kyphoscoliosis, and enlarged liver and sometimes enlarged spleen are the other important clinical findings. Radiographic abnormalities include subperiosteal bone formation, midshaft widening and demineralization of long bones, and hypoplasia and beaking of the thoracolumbar vertebrae. Vacuoles are seen in 10 to 80 percent of blood lymphocytes and foam cells in the urinary sediment.
A partial or complete deficiency of beta-galactosidase and accumulation of GM1 ganglioside in the viscera and in neurons and glia cells throughout the CNS are the specific biochemical abnormalities. In addition, the epithelial cells of renal glomeruli, histiocytes of the spleen, and liver cells contain a modified keratan sulfate and a galactose-containing oligosaccharide. The changes in the bone are also like those in the Hurler form of mucopolysaccharidosis. The disease should be suspected in an infant having the facial features of mucopolysaccharidosis and severe early-onset neurologic abnormalities.
A remarkably benign variant, also inherited as an autosomal recessive trait, begins later in childhood but may advance so slowly as to allow attainment of adult life. Dystonia, myoclonus, seizures, visual impairment, and macular red spots were features of the two cases described by Goldman and coworkers.
Globoid Cell Leukodystrophy (Krabbe Disease, Galactocerebrosidase Deficiency, GALC Mutation)