There may be other types of such leukodystrophies with sudanophilic pathology that do not appear to be
Pelizaeus-Merzbacher disease. They are also characterized by psychomotor regression; spastic paralysis; incoordination; blindness and optic atrophy; seizures (rare); severe microcephaly. Diffuse degeneration of myelinated fibers (visible by MRI) with phagocytosis of the sudanophilic products of myelin and gliosis are the major changes.
Spongy Degeneration of Infancy (Canavan-van Bogaert-Bertrand or Canavan Disease, ASPA Mutation)
This is an autosomal recessive leukodystrophy that was described in 1931 by Myrtelle Canavan as a form of
Schilder disease (see Chap. 35), but later categorized as a special spongy degeneration of the brain by van Bogaert and Bertrand. Of 48 affected families reported by Banker and Victor, 28 were of Jewish ancestry. Onset is early, usually recognizable in the first 3 months of life and sometimes in the first neonatal weeks. There is either a lack of development or rapid regression of psychomotor function, loss of sight and optic atrophy, lethargy, difficulty in sucking, irritability, reduced motor activity, hypotonia followed by spasticity of the limbs with corticospinal signs, and an enlarged head (macrocephaly). There are no visceral or skeletal abnormalities but a variable sensorineural hearing loss has been found (Ishiyama et al). Seizures occur in some cases. An interesting but unexplored aspect of the disease is the occurrence of blond hair and light complexion in affected members, in contrast to the darker hair and complexion of their normal siblings (Banker and Victor).
The CSF is usually normal but the protein concentration is slightly elevated in some cases. The disease is characterized by an increased urinary excretion of N-acetyl-l-aspartic acid (NAA), which may be used as a biochemical marker, a feature also evident on MR spectroscopy of the brain. It reflects the basic enzyme abnormality, a deficiency of aminoacylase II, which catalyzes the breakdown of NAA (Matalon et al). On CT there is attenuation of cerebral and cerebellar white matter in an enlarged brain with relatively normal-size ventricles. The MRI appearance (Fig. 36-3) is that of diffuse, somewhat uneven, high signal intensity on T2-weighted images. A leukodystrophy with behavioral regression, an enlarging head, a characteristic MRI abnormality, and a marked elevation of urinary NAA should leave little doubt about the diagnosis. The closest phenotype is Tay Sachs disease.
The characteristic pathologic changes are an increase in brain volume (and weight), spongy degeneration in the deep layers of the cerebral cortex and subcortical white matter, widespread depletion of myelin involving the convolutional more than the central white matter, loss of Purkinje cells, and hyperplasia of Alzheimer type II astrocytes throughout the cerebral cortex and basal ganglia. Adachi and coworkers have demonstrated an abnormal vacuolar accumulation of fluid in astrocytes and between split myelin lamellae; they have suggested that the loss of myelin is secondary to these changes.
The enlargement of the brain in this disease must be distinguished clinically from GM2 gangliosidosis, Alexander disease, Krabbe disease, and nonprogressive megalocephaly and pathologically from a variety of disorders characterized by vacuolation of nervous tissue. There is no treatment.