Ocular abnormalities of specific diagnostic value in this age group are as follows: 1. Rapid pendular nystagmus: Pelizaeus-Merzbacher disease, rarely Krabbe leukodystrophy, Cockayne syndrome (later age) 2. Macular cherry-red spots: Tay-Sachs disease and Sandhoff variant, some cases of infantile Niemann-Pick disease, and rarely lipofuscinosis (see Table 36-4) 3. Corneal opacification: Lowe disease, infantile GM1 gangliosidosis; later, the mucopolysaccharidoses 4. Cataracts: galactosemia, Lowe disease, Zellweger disease (also congenital rubella)
Several other medical findings are of specific diagnostic value: 1. Dysmorphic facies: generalized GM1 gangliosidosis, Lowe and Zellweger syndromes, and some early cases of mucopolysaccharidosis and mucolipidosis 2. Enlarged liver and spleen: infantile Gaucher disease and Niemann-Pick disease; one type of hyperammonemia; Sandhoff disease; later, the mucopolysaccharidoses and mucolipidoses 3. Enlarging head without hydrocephalus (macrocephaly): Canavan spongy degeneration of infancy, some cases of Tay-Sachs disease, Alexander disease 4. Beaking of vertebral bodies in radiographs: GM1 gangliosidosis (and, at a more advanced age, the mucopolysaccharidoses, fucosidosis, mannosidosis, and the mucolipidoses) 5. Multiple arthropathies and raucous dysphonia: Farber disease 6. Storage granules and vacuolated lymphocytes: Niemann-Pick disease, generalized GM1 gangliosidosis 7. Abnormal histiocytes in marrow smears: Gaucher cells, foamy histiocytes in Niemann-Pick disease, generalized GM1 gangliosidosis and closely related diseases, Farber disease 8. Colorless, friable hair: Menkes disease
Included here are the diseases that become manifest between the ages of 1 and about 4 years. Diagnosis is less difficult than in the neonate and young infant. A pathologic process in the nervous system is reliably ascertained by the obvious progression of a neurologic disorder, such as a loss of ability to walk and to speak, which usually parallels a regression in other high-level (quasi-intellectual) functions. Embryologic anomalies, prenatal diseases, and birth injuries can be excluded with relative certainty if psychomotor development was normal in the first year or two. Diseases characterized by seizures and myoclonus may prove more difficult to interpret, for the seizures may occur at any age from a variety of distant or immediate neurologic causes and, if frequent, may cause a significant impairment of psychomotor function. The effects of anticonvulsant medications may add to the impairment of cortical function. Unfortunately, most of the slowly advancing metabolic diseases of the second year may be so subtle in their effects that for a time the physician cannot be sure whether a regression of intellectual functions is taking place or mental retardation or autism is becoming apparent for the first time. An added difficulty arises when, for a number of years, the hereditary metabolic abnormality merely slows development. Repeated examinations and testing will usually settle the matter. Suspicion of a progressive encephalopathy is heightened by the presence of certain ocular, visceral, and skeletal abnormalities, as described below.