This group of metabolic disorders presents many of the same diagnostic problems as those of early infancy. The flow chart in Fig. 36-6, which divides these disorders into dysmorphic, visceromegalic, and purely neurologic groups, is equally useful in the differential diagnosis of both age groups. As with the early infantile diseases, certain clusters of neurologic, skeletal, dermal, ophthalmic, and laboratory findings are highly distinctive and often permit the identification of a particular disease. These signs are listed below: 1. Evidence of involvement of peripheral nerves (weakness, hypotonia, areflexia, sensory loss, reduced conduction velocities) in conjunction with lesions of the CNS—metachromatic leukodystrophy, Krabbe leukodystrophy, neuroaxonal dystrophy, and Leigh disease 2. Ophthalmic signs a. Corneal clouding—several of the mucopolysaccharidoses (Hurler, Scheie, Morquio, Maroteaux-Lamy), mucolipidoses, tyrosinemia, aspartylglycosaminuria (rare) b. Cherry-red macular spot—GM2 gangliosidosis, GM1 gangliosidosis (half the cases), lipomucopolysaccharidosis, occasionally Niemann-Pick disease c. Retinal degeneration with pigmentary deposits—Jansky-Bielschowsky lipid storage disease, GM1 gangliosidosis, syndrome of sea-blue histiocytes d. Optic atrophy and blindness—metachromatic leukodystrophy, neuroaxonal dystrophy e. Cataracts—Marinesco-Sjögren syndrome, Fabry disease, mannosidosis f. Ocular apraxia—ataxia-telangiectasia, Niemann-Pick disease g. Impairment of vertical eye movements—late infantile Niemann-Pick disease, juvenile dystonic lipidosis, sea-blue histiocyte syndrome, Wilson disease h. Jerky eye movements, limited abduction—late infantile Gaucher disease 3. Extrapyramidal signs—late-onset Niemann-Pick disease (rigidity, abnormal postures), juvenile dystonic lipidosis (dystonia, choreoathetosis), Rett, ataxia- telangiectasia (athetosis), Sanfilippo mucopolysaccharidosis, type I glutaric acidemia, Wilson disease, Segawa dopa-responsive dystonia 4. Facial dysmorphism—Hurler, Scheie, Morquio, and Maroteaux-Lamy forms of mucopolysaccharidosis, aspartylglycosaminuria, mucolipidoses, GM1 gangliosidosis, mannosidosis, fucosidosis (some cases), multisulfatase deficiencies (Austin), some mitochondrial disorders 5. Dwarfism, spine deformities, arthropathies—Hurler, Morquio, and other mucopolysaccharidoses, Cockayne 6. Enlarged liver and spleen—Niemann-Pick disease, Gaucher disease, all mucopolysaccharidoses, fucosidosis, mucolipidoses, GM1 gangliosidosis 7. Alterations of skin—photosensitivity (Cockayne syndrome and one form of porphyria); papular nevi and angiokeratoma (Fabry disease, fucosidosis); telangiectasia of ears, conjunctiva, chest (ataxia- telangiectasia); ichthyosis (Sjögren-Larsen disease, caused by fatty alcohol dehydrogenase deficiency); plaque-like lesions in Hunter syndrome 8. Beaked thoracolumbar vertebrae—all mucopolysaccharidoses, mucolipidoses, mannosidosis, fucosidosis; aspartylglycosaminuria, multiple sulfatase deficiencies 9. Deafness—mucopolysaccharidoses, mannosidosis, Cockayne syndrome 10. Hypertrophied gums—mucolipidoses, mannosidosis 11. Vacuolated lymphocytes—all mucopolysaccharidoses, mucolipidoses, mannosidosis, fucosidosis 12. Granules in neutrophils—all mucopolysaccharidoses, mucolipidoses, mannosidosis, fucosidosis, multiple sulfatase deficiencies