Lysosomal Carbohydrate Diseases

Deficiencies of lysosomal enzymes necessary for the degradation of complex carbohydrates result in an accumulation of nondegraded products in various tissues and cells. Such products are the mucopolysaccharides, the mucolipids, the glycoproteins, and the glycogen. The diseases affect chiefly infants and children. Despite genetic and enzymatic heterogeneity, many diseases share facial and skeletal abnormalities, multiorgan manifestations, and urinary excretion of abnormal metabolites, mucopolysaccharides, mucolipids, and glycoproteins (Table 9.4).

Neuronal Ceroid Lipofuscinosis Pas Stain

figure 9.5

Late infantile neuronal ceroid lipofuscinosis. This boy's disease began at 3 years of age, when he had his first generalized tonic-clonic seizure and his gait became unsteady. At 4 years of age, he developed jerking movements in his body and extremities. He gradually lost his motor skills and language. By age 5 years, he was blind, unresponsive, unable to hold his head up or sit, and displayed constant myoclonic jerks. At age 6 years, he died. A. Transverse section of the brain at thalamus level shows severe generalized cortical and white matter atrophy and enlarged ventricles. B. The cerebral cortex, totally depleted of neurons, is spongy. C. The medullary neurons are swollen (Cresyl-violet) and (D) filled with PAS positive material (PAS stain). E. The cerebellar cortex is depleted of Purkinje cells and granule cells. Instead, a prominent astrocytic layer outlines the site of lost Purkinje cells (Cresyl-violet). F. Both optic nerves are degenerated (Weil stain).

figure 9.5

Late infantile neuronal ceroid lipofuscinosis. This boy's disease began at 3 years of age, when he had his first generalized tonic-clonic seizure and his gait became unsteady. At 4 years of age, he developed jerking movements in his body and extremities. He gradually lost his motor skills and language. By age 5 years, he was blind, unresponsive, unable to hold his head up or sit, and displayed constant myoclonic jerks. At age 6 years, he died. A. Transverse section of the brain at thalamus level shows severe generalized cortical and white matter atrophy and enlarged ventricles. B. The cerebral cortex, totally depleted of neurons, is spongy. C. The medullary neurons are swollen (Cresyl-violet) and (D) filled with PAS positive material (PAS stain). E. The cerebellar cortex is depleted of Purkinje cells and granule cells. Instead, a prominent astrocytic layer outlines the site of lost Purkinje cells (Cresyl-violet). F. Both optic nerves are degenerated (Weil stain).

Weil Stain

figure 9.6

Juvenile neuronal ceroid lipofuscinosis. The disease of a 6-year-old girl began with failing eyesight. Over the years, her mental functions, motor skills, and speech progressively deteriorated. After an 8-year clinical course, she died. A. The brain shows a moderately severe cortical atrophy. B. The cerebellum shows Purkinje cell losses and storage of PAS-positive material in remaining Purkinje cell and dendrites (PAS stain).

figure 9.6

Juvenile neuronal ceroid lipofuscinosis. The disease of a 6-year-old girl began with failing eyesight. Over the years, her mental functions, motor skills, and speech progressively deteriorated. After an 8-year clinical course, she died. A. The brain shows a moderately severe cortical atrophy. B. The cerebellum shows Purkinje cell losses and storage of PAS-positive material in remaining Purkinje cell and dendrites (PAS stain).

Purkinje Cell Degeneration

figure 9.7

Adult ceroid lipofuscinosis. Difficulty walking was the presenting symptom in a 57-year-old man. Examination revealed a moderate weakness with increased extensor tone, brisk reflexes, and Babinski signs in the legs, and a mild dysmetria and coarse intention tremor in the arms and hands. Vision, sensation, and autonomic functions were normal. Over the years, his weakness slowly progressed and, by age 63, he was wheelchair bound. Around the same time, he had his first grand mal seizure and developed myoclonic jerks. EEG was abnormal with spike and photomyoclonic discharges, and MRI displayed severe cerebellar atrophy. Psychological testing revealed mild memory and cognitive deficits. Over the next few years, he became bedridden, dysphagic, and dysarthric and myoclonic jerks were constant. After a 13-year clinical course, he died at age 70 years. A. EEG shows photomyoclonic responses. B. MRI shows marked cerebellar atrophy. C. The cerebellar cortex is severely atrophic. D. The neurons in the hippocampus are distended with PAS-positive material. E. The cerebellar cortex shows Purkinje cell losses (HE) and (F) freely dispersed LFB-positive granules at the site of disintegrated Purkinje cells (LFB stain).

figure 9.7

Adult ceroid lipofuscinosis. Difficulty walking was the presenting symptom in a 57-year-old man. Examination revealed a moderate weakness with increased extensor tone, brisk reflexes, and Babinski signs in the legs, and a mild dysmetria and coarse intention tremor in the arms and hands. Vision, sensation, and autonomic functions were normal. Over the years, his weakness slowly progressed and, by age 63, he was wheelchair bound. Around the same time, he had his first grand mal seizure and developed myoclonic jerks. EEG was abnormal with spike and photomyoclonic discharges, and MRI displayed severe cerebellar atrophy. Psychological testing revealed mild memory and cognitive deficits. Over the next few years, he became bedridden, dysphagic, and dysarthric and myoclonic jerks were constant. After a 13-year clinical course, he died at age 70 years. A. EEG shows photomyoclonic responses. B. MRI shows marked cerebellar atrophy. C. The cerebellar cortex is severely atrophic. D. The neurons in the hippocampus are distended with PAS-positive material. E. The cerebellar cortex shows Purkinje cell losses (HE) and (F) freely dispersed LFB-positive granules at the site of disintegrated Purkinje cells (LFB stain).

table 9.4.

Lysosomal Diseases with Phenotypic Resemblance to MSP-I

GM1 Gangliosidosis

MLD with multiple sulfatase deficiency

Mucolipidosis

MLII (I-cell disease) MLIII Glycoproteinosis Mannosidosis Fucosidosis Aspartylglucosaminuria Sialuria Infantile

MSP, mucopolysaccharidosis; MLD, metachromatic leukodystrophy

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