The clinical, pathological and biochemical findings in two brothers with a newly recognized form of infantile neuroaxonal dystrophy associated with alpha-N-acetylgalactosaminidase deficiency are reported from the Divisions of Medical and Molecular Genetics and Neuropathology, Mount Sinai School of Medicine, New York; Department of Chemistry, University of Alberta, Edmonton, Canada; Department of Physiological Chemistry, University of Bonn, Federal Republic of Germany; and Department of Hunan Genetics, University of Wurzburg, Federal Republic of Germany. The brothers were the offspring of fifth cousins of German descent and their early development was normal. In the older brother, the clinical onset of disease was signaled by poor coordination of gait, clumsiness, and episodes of falling at 12 months. In the younger brother, grand mal seizures began at eight months and occurred five times over the next six months. Each had a regressive course beginning after 15 months of age, with loss of all mental and motor skills acquired previously. Strabismus, nystagmus, visual impairment, muscular hypotonia, and frequent myoclonic movements developed in both. By three to four years of age, both brothers had profound psychomotor retardation and spasticity, and were immobile and incontinent. CT and MRI showed atrophy of the cerebellum, brain stem and cervical spinal cord, with lesser atrophic changes in the cerebral gray and white matter, optic tracts and cranial nerves. EEG revealed multifocal isolated spikes and spike wave complexes. The urinary oligosaccharide profile was abnormal, suggesting the possibility of a lysosomal disease. The activity of alpha-N-acetylgalactosaminidase was deficient whereas 21 other lysosomal enzymes were normal. [1]

COMMENT. The neuroaxonal dystrophies include the infantile (Seitelberger's disease, late-infantile, and juvenile forms, neuroaxonal leukodystrophy, and Hallervorden-Spatz syndrome) and all are characterized by the spheroids in the terminal endings of axons in the central nervous system. The axonal dystrophy in alpha-N-acetylgalactosaminidase deficiency described in this article differs from that observed in other lysosomal storage diseases. The absence of identifiable lysosomal storage in this newly described disorder suggests a causal relation between the enzyme deficiency and the resultant axonal pathology. A report from the Departments of Pediatrics, Radiology and Neurology, Kyoto, Japan, suggests that magnetic resonance imaging may be useful in the diagnosis and classification of infantile neuroaxonal dystrophy [2]. A six year old boy with typical clinical features of infantile neuroaxonal dystrophy showed increased metal deposition in the globus pallidus and MRI findings of Hallervorden-Spatz syndrome suggesting that these two disease entities overlap. The “eye of the tiger” sign was described in the MRI of two patients with Hallervorden-Spatz syndrome and dystonia. (See Ped Neur Briefs, October 1988, 2:77).