IEM AND ACQUIRED METABOLIC Flashcards
What structure?
_________a histologic hallmark of storage diseases. The perikaryon is large, pear shaped. The nucleus and some residual Nissl substance are displaced toward the apical dendrite
Ballooned cortical pyramidal neuron,
summary of lysosomal storage diseases
summary of GM2 Gangliosidosis
A fi rst-born infant girl of healthy Ashkenazi Jewish parents developed normally up to 6 months of age, when she became listless and unresponsive to her environment. A few months later, cherry red spot of the macula was diagnosed. She startled in response to all stimuli and developed seizures. She steadily regressed to a vegetative state and, at 20 months of age, she died.
A. The brain is large, weighing 1,400 g.
B. Frozen section of the cerebral cortex shows accumulation of glycolipids in the neurons (oil-red O stain). C. Cerebellum shows Purkinje cell losses and expansion of empty-appearing dendrites due to extraction of lipids during tissue processing (Bodian stain).
D. Autonomic ganglia in rectal mucosa contain lipid material (Oilred O).
E. Schematic drawing of concentric lamellar bodies, the EM appearance of storage material
Tay Sachs
Ballooned Purkinje cells in the cerebellum with distended dendrites (HE)
Niemann-Pick disease
WHAT ARE THESE?
Gaucher’s disease. Gaucher cell in the hemispheric white
matter (HE).
This boy’s disease began at 3 years of age, when he had his fi rst generalized tonicclonic 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) fi lled 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).
Late infantile 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).
Juvenile neuronal ceroid lipofuscinosis
WHAT DSE?
A and B. Pictures of a mentally retarded girl show the characteristic facial and skeletal features of the disease at ages 9 and 13 years. At age 13, she died of pulmonary infection. Note the short stature, large head, coarse facial features, Thick tongue, and short neck. C. Transverse section of the brain shows dilated ventricles, focal thickening of the leptomeninges, and dilated perivascular spaces. D. Neuronal storage of PAS-positive material is moderate (PAS stain). E. The dilated pericapillary spaces are fi lled with a fi ne mesenchymal network (HE).
Hurler’s disease
Glycogen is stored (A) in the neurons and (B) astrocytes (frozen section, PAS stain).
POMPE’S DISEASE
Loose perivascular lymphocytic infi ltrations and reactive astrocytes are present in the hemispheric
white matter (HE).
ADRENOLEUKODYSTROPHY
SUMMARY OF ETIOLOGY OF LEUKODYSTROPHY
WHAT DISEASE?
The disease of an 8-year-old boy began with a decline in his school performance, daydreaming, and aimless scribbling. At age 11, he had his fi rst grand mal seizure. Over the ensuring years, his mental and motor functions rapidly deteriorated. First, he became speechless and unable to stand or walk; then he became bedridden, with his extremities in fl exion contractures. After a 12-year course, at age 20 years, he died. His younger sister developed a similar illness and died before him.
A and B. On transverse sections the hemispheric white matter from the frontal to the occipital lobes is reduced in volume, sunken, yellow, and gelatinous. C. Occipital lobe shows total loss of myelin and relative sparing of arcuate fi bers. D. Myelin loss is total in the cerebellum and almost total in the pons (Weil stain). E. Brown, metachromatically stained myelin breakdown products are abundant in the subcortical white matter. F. Peripheral nerve shows myelin degeneration with metachromatic granules. G. Metachromatic granules are present in tubular epithelium of kidney (acidic Cresyl-violet).
Juvenile metachromatic leukodystrophy
A. Single and clustered globoid cells are dispersed in
the demyelinated cerebral hemisphere.
B. Higher magnifi cation view of multinucleated
globoid cells (HE).
Globoid leukodystrophy
a 6-year-old profoundly retarded, blind, quadriplegic,
macrocephalic boy.
A. Transverse sections from the 1,465 g brain shows markedly reduced and soft hemispheric white matter.
B. There is total absence of myelin in the frontal lobe (Weil
stain).
C. The white matter is vacuolated and spongy.
D. The cerebellar white matter, and to some extent the
cortex, are vacuolated and spongy
Canavan’s disease
Rosenthal fi bers are concentrated around a blood vessel and are also diffusely dispersed in the white
matter (HE).
Alexander’s disease
A. The liver is small and cirrhotic and shows (B) atrophy of the hepatic lobules and prominent perilobular fi brosis (HE).
C. The hippocampus shows extensive neuronal losses. D. Severe Purkinje cell losses are present in the cerebellum (Cresyl-violet).
E. Basal ganglia shows basophilic mineral granules in vessel’s wall and parenchyma (HE).
Galactosemia.
An infant girl developed normally until 1 year of age, when she began to stumble and gradually lost her ability to walk. At 3 years of age, she was speechless, had pale optic discs, searching nystagmus, and stiff extremities. Over the ensuing years, she developed seizures and myoclonic jerks. At nine and a half years of age, she died.
Thalamus shows (A) eosinophilic (HE) and (B) argyrophilic axonal spheroids (Bodian stain). C. Basophilic-iron–positive granules are deposited in basal ganglia (HE). D. The cerebellum shows extensive Purkinje cell losses (HE). E. Peripheral nerve shows myelin degeneration and small axonal spheroids (LFB-CV).
Neuroaxonal dystrophy with iron deposition
Schematic drawing of distribution of lesions of what disease?
Wernicke-Korsakoff encephalopathy
Nervous System Manifestations in
Major Vitamin Defi ciencies
a 48-year-old man, a heavy drinker.
A. Transverse section at thalamus level shows brownish discoloration of the mammillary bodies and fresh petechiae
in the fl oor of the third ventricle.
Macrosections show (B) hypercellularity in mammillary bodies due to proliferated astrocytes and macrophages (Cresylviolet), and (C) demyelination of stria medullaris and pallor of myelin in the thalami (Weil stain). D. Mammillary body contains macrophages and proliferated astrocytes (HE).
Wernicke-Korsakoff encephalopathy
A. Transverse section at midbrain level shows hemorrhagic necrosis in dorsomedial aspects of pulvinars (habenular nuclei), grayish discoloration of ventricular wall and brownish-tan discoloration of lateral geniculate bodies,
B. Upper pons shows hemorrhagic discoloration of locus ceruleus.
C. Medulla shows symmetrically situated hemorrhages in the fl oor of fourth ventricle and
(D) necrosis at the sites of hypoglossus nuclei (HE).
Wernicke-Korsakoff encephalopathy
Macrosection of the lumbar spinal cord shows spongy degeneration of myelin in the posterior columns and corticospinal tracts of the lateral columns (Weil stain).
WHAT DSE?
Subacute combined degeneration of the spinal cord in vitamin B12 defi ciency
a 53-year-old chronic alcoholic man with severe liver cirrhosis.
Alzheimer type 2 astrocytes in basal ganglia display (A) large vesicular nuclei, scanty chromatin, and prominent nucleoli (HE), and (B) positive immunostaining for S-100 protein (Immunostain). C. The subcortical white matter shows focal spongiosis (HE).
HEPATIC ENCEPH
