Page 278 - Textbook of Pathology, 6th Edition

262 deranged glucose metabolism are hyperuricaemia and Clinically, 3 subtypes of Gaucher’s disease are identified
accumulation of pyruvate and lactate. based on neuronopathic involvement:
The disease manifests clinically in infancy with failure to Type I or classic form is the adult form of disease in which
thrive and stunted growth. Most prominent feature is there is storage of glucocerebrosides in the phagocytic cells
enormous hepatomegaly with intracytoplasmic and of the body, principally involving the spleen, liver, bone
intranuclear glycogen. The kidneys are also enlarged and marrow, and lymph nodes. This is the most common type
show intracytoplasmic glycogen in tubular epithelial cells. comprising 80% of all cases of Gaucher’s disease.
Other features include gout, skin xanthomas and bleeding Type II is the infantile form in which there is progressive
tendencies due to platelet dysfunction.
involvement of the central nervous system.
SECTION I
POMPE’S DISEASE (TYPE II GLYCOGENOSIS). This is Type III is the juvenile form of the disease having features
also an autosomal recessive disorder due to deficiency of a in between type I and type II i.e. they have systemic
lysosomal enzyme, acid maltase, and is the only example of involvement like in type I and progressive involvement of
lysosomal storage disease amongst the various types of the CNS as in type II.
glycogenoses. Acid maltase is normally present in most cell The clinical features depend upon the clinical subtype of
types and is responsible for the degradation of glycogen. Its Gaucher’s disease. In addition to involvement of different
deficiency, therefore, results in accumulation of glycogen in organs and systems (splenomegaly, hepatomegaly,
many tissues, most often in the heart and skeletal muscle, lymphadenopathy, bone marrow and cerebral involvement),
leading to cardiomegaly and hypotonia. a few other features include pancytopenia, or thrombo-

McARDLE’S DISEASE (TYPE V GLYCOGENOSIS). The cytopenia secondary to hypersplenism, bone pains and
condition occurs due to deficiency of muscle phosphorylase pathologic fractures.
resulting in accumulation of glycogen in the muscle Microscopy shows large number of characteristically
(deficiency of liver phosphorylase results in type VI
glycogenosis). The disease is common in 2nd to 4th decades distended and enlarged macrophages called Gaucher cells
which are found in the spleen, liver, bone marrow and
of life and is characterised by painful muscle cramps, lymph nodes, and in the case of neuronal involvement, in
especially after exercise, and detection of myoglobinuria in the Virchow-Robin space. The cytoplasm of these cells is
half the cases.
abundant, granular and fibrillar resembling crumpled
Mucopolysaccharidoses (MPS) tissue paper. They have mostly a single nucleus but
occasionally may have two or three nuclei (Fig. 10.5, A,
Mucopolysaccharidoses are a group of six inherited C). Gaucher cells are positive with PAS, oil red O, and
General Pathology and Basic Techniques
syndromes numbered from MPS I to MPS VI. Each of these Prussian-blue reaction indicating the nature of
results from deficiency of specific lysosomal enzyme accumulated material as glycolipids admixed with
involved in the degradation of mucopolysaccharides or haemosiderin. These cells often show erythrophagocytosis
glycosaminoglycans, and are, therefore, a form of lysosomal and are rich in acid phosphatase.
storage diseases. Mucopolysaccharides which accumulate in
the MPS are: chondroitin sulphate, dermatan sulphate,
heparan sulphate and keratan sulphate. All these syndromes Niemann-Pick Disease
are autosomal recessive disorders except MPS II (Hunter’s This is also an autosomal recessive disorder characterised
syndrome) which has X-linked recessive transmission. by accumulation of sphingomyelin and cholesterol due to
Syndrome of MPS manifests in infancy or early childhood defect in acid sphingomyelinase.
and involves multiple organs and tissues, chiefly connective Two types have been described: type A and B.
tissues, liver, spleen, bone marrow, lymph nodes, kidneys, Type A is more common and typically presents in infancy
heart and brain. The mucopolysaccharides accumulate in and is characterised by hepatosplenomegaly, lymph-
mononuclear phagocytic cells, endothelial cells, intimal adenopathy, rapidly progressive deterioration of CNS and
smooth muscle cells and fibroblasts. The material is finely physical underdevelopment. About a quarter of patients
granular and PAS-positive by light microscopy. By electron present with familial amaurotic idiocy with characteristic
microscopy, it appears in the swollen lysosomes and can be cherry-red spots in the macula of the retina (amaurosis = loss
identified biochemically as mucopolysaccharide.
of vision without apparent lesion of the eye).
Gaucher’s Disease Type B develops later and has a progressive hepato-
This is an autosomal recessive disorder in which there is splenomegaly with development of cirrhosis due to
mutation in lysosomal enzyme, acid β-glucosidase (earlier replacement of the liver by foam cells, and impaired lung
called glucocerebrosidase), which normally cleaves glucose function due to infiltration in lung alveoli.
from ceramide. This results in lysosomal accumulation of Microscopy shows storage of sphingomyelin and choles-
glucocerebroside (ceramide-glucose) in phagocytic cells of terol within the lysosomes, particularly in the cells of
the body and sometimes in the neurons. The main sources mononuclear phagocyte system. The cells of Niemann-
of glucocerebroside in phagocytic cells are the membrane Pick disease are somewhat smaller than Gaucher cells
glycolipids of old leucocytes and erythrocytes, while the and their cytoplasm is not wrinkled but is instead foamy
deposits in the neurons consist of gangliosides.