Niemann-Pick Disease

This is also an autosomal recessive disorder characterized by accumulation of sphingomyelin and cholesterol. Majority of the cases (about 80%) have deficiency of sphingomyelinase which is required for cleavage of sphingomyelin, while a few cases probably result from deficiency of an activator protein.

The condition presents in infancy and is characterized by hepatosplenomegaly, lymphadenopathy and physical and mental underdevelopment. About a quarter of patients present with familial amaurotic

idiocy with characteristic cherry-red spots in the macula of the retina.

The storage of sphingomyelin and cholesterol occurs within the lysosomes, particularly in the cells of mononuclear phagocyte system. The cells of Niemann-Pick disease are somewhat smaller than Gaucher cells and their cytoplasm is not wrinkled but is instead foamy and vacuolated which stains positively with fat stains. These cells are widely distributed in the spleen, liver, lymph nodes, bone marrow, lungs, intestine and brain.

GLUCOGENOSES

Disease Enzyme Organs in which pathologic products accumulate
Gierke's (typel) Glucose-6-phosphatas Liver, kidneys
Pompe's (type 2) Acid -L-glucosidase Muscles
MacArdle's (type 5) System of muscles's phosphorilas Muscles
Hers, (type 6) Liver's phosphorilas Liver
Forbes-Cori (type 3) Amylo-1,6-glucosidase Liver, muscles, heart
Andersen's (type 4) Amylo-1,4-1,6-trans-glucosidase Liver, spleen, lymphatic glands

In the type 1, 2, 5, 6 - the structure of glycogen in the tissues is not changed. In the type 3,4 - glycogen structure is changed.

Gierke's disease(type 1)

This condition is inherited as an autosomal recessive disorder due to deficiency of enzyme, glucose-6-phosphatase. In the absence of glucose-6-phosphatase, excess of normal type of glycogen accumulates in the liver and also results in hypogly-caemia due to reduced formation of free glucose from glycogen. As a results, fat is metabolized for energy requirement leading to hyperlipoproteinemia and ketosis. Other changes due to deranged glucose metabolism are hyperuricaemia and accumulation of pyruvate and lactate.

The disease manifests clinically in infancy with failure to thrive and stunted growth. Most prominent feature is enormous hepatomegaly with intra-cytoplasmic and intranuclear glycogen. The kidneys are also enlarged and show intracytoplasmic glycogen in tubular epithelial cells. Other features include gout, skin xanthomas and bleeding tendencies due to platelet dysfunction.

Pompe's disease(type II)

This is also an autosomal recessive disorder due to deficiency of a lysosomal enzyme, acid maltase, and is the only example of lysosomal storage disease amongst the various types of glycogenoses. Acid maltase is normally present in most cell types and is

responsible for the degradation of glycogen. Its deficiency, therefore, results in accumulation of glycogen in many tissues, most often in the heart and skeletal muscl, leading to cardiomegaly and hypotonia.

Me Ardle's disease (typeV)

The condition occurs due to deficiency of muscle phosphorylase resulting in accumulation of glycogen in the muscle (deficiency of liver phosphorylase results in type VI glycogenoses). The disease is common in 2nd to 4th decades of life and is characterized by painful muscle cramps, especially after exercise, and detection of myoglobinuria in half the cases.

The outcome of storage diseases is unfavorable because of insufficient development of the respective organ.

STROMAL INFILTRATION OFFAT

Neutral fat metabolism disturbance.Neutral (labile) fat which accounts for energy consumption is normally localized in the fat depots: subcutaneous fat, mesentery, omentum, subepicardial and perinephral spaces as well as in the bone marrow.

Disturbance in neutral fat metabolism may be associated with increase or reduction of its supply in the fat depots as well as appearance of fat in the places where it is not present under normal conditions, e.g. among cardiomyocytes.

The increase in neutral fat amount is called obesity. As a rule it is a generalized process when the amount of fat in the depots increases. Depending on the excess of the patient mass compared to the norm, 4 degrees of obesity are defined. If the patient mass increases by 20 - 29% we distinguish 1st degree of obesity, if the patient's mass increases by 30 - 49% 2nd degree, if the patient's mass increases by 50 - 99% 3rd degree; if the patient's mass increases by 100% and more 4th degree of obesity. As a rule, in such patients fat is found in the places where it is not present under normal conditions, e.g. in the myocardium, pancreas. The damage to these organs is most serious. Subepicardial fat covers the heart as a case, invades the myocardial stroma causing atrophy and sclerosis called cardiosclerosis. If the connective tissue does not grow, heart rupture in the area of fat growth may occur. In pancreatic lipomatosis beta-cell atrophy and diabetes mellitus are possible.

According to the etiology the following types of obesity are defined: 1) primary (idiopathic), 2) secondary.

There are several types of secondary obesity: a) alimentary, b) cerebral, c) endocrine, d) hereditary in Gierke's disease.

According to the patient's appearance, obesity may be symmetrical, upper, medial, lower.

According to morphological peculiarities of adipose tissue, it may be hypertrophic or hyperplastic.

In hypertrophic type adipose tissue enlarges due to increased volume of fatty cells, in hyperplastic due to increase in their number. Obesity is a severe complication of mainly endocrine and nervous diseases. Alimentary obesity is also unfavorable for the organism. As a rule such patients develop ischemic heart disease.

Local enlargement of adipose tissue (lipomatosis) occurs in Dercum's disease when painful fat nodes appear in the subcutaneous fat of the lower and upper extremities and trunk.

Sharp reduction in the amount of neutral fat in the whole organism is observed in inanition and cachexia or skeletization. Besides reduction in neutral fat amount there is dystrophy and atrophy of inner parenchymal organs.

Disturbance in cholesterol and its ethers metabolismcauses atherosclerosis (See Atherosclerosis).