The following points highlight the six major diseases caused due to errors in lipid metabolism. The diseases are: 1. Gaucher’s Disease 2. Niemann-Pick Disease 3. Tay-Sach’s Disease 4. Fabry’s Disease 5. Refsum’s Disease 6. Krabbe’s Disease.
Errors in Lipid Metabolism: Disease # 1. Gaucher’s Disease:
In this disease, the cerebroside content of the reticuloendothelial cells (e.g., spleen) is very high. In the cerebroside molecule, the kerasin is characterized by glucose replacing galactose.
The concentrations of cerebrosides are much higher in medullated than non-medullated nerve fibers. The symptoms of this disease are mentioned below. The disease is caused by the deficiency of glucosyl ceremide hydrolase or glucocerebrosidase.
a. The spleen is significantly increased and there are signs of leukopenia and thrombocytopenia.
b. The liver is enlarged and the marrow cavity is widened.
c. Eyes show a yellow-brown wedge-shaped elevation.
d. In early infantile form, the disease starts early and death occurs before attaining the age of 2 years. Neurological symptoms are usually present.
Errors in Lipid Metabolism: Disease # 2. Niemann-Pick Disease:
In this disease, excessive amounts of sphingomyelin are deposited in spleen, brain and liver. This results in the deficiency of sphingomyelinase. The hereditary disease is found in infancy and death occurs within the first two years of life.
The clinical findings are:
a. Enlarged liver and spleen.
b. Mental retardation and fatal in early life.
c. Anemia and leukocytosis.
d. The nervous system is affected.
e. A cherry red spot may be seen over the retina.
f. Cholesterol deposits in the tissues are increased.
Errors in Lipid Metabolism: Disease # 3. Tay-Sach’s Disease:
This disease is characterized by the increased accumulation of Gangliosides (GM2) in brain and spleen.
The characteristic clinical symptoms are:
a. Mental retardation, blindness and muscular weakness.
b. A cherry red spot appears in the muscular region of the eye within the first year of life.
c. At about two years of age, the circumference of the head becomes 50 per cent greater than normal.
d. There is repeated respiratory tract infections of the patient and the patient expires at the third or fourth year.
Errors in Lipid Metabolism: Disease # 4. Fabry’s Disease:
In this disease, large amounts of ceramide trihexoside are accumulated in the kidney. The deficiency of the enzyme ceramide trihexosidase causes this disease.
The clinical findings are:
a. Skin rash and kidney failure.
b. Male patients generally die due to progressive renal failure in the fourth or fifth decade of life.
c. Cardiac enlargement and edema of the extremities.
d. Some patients suffer from excessive pain in the joints.
e. Corneal opacities and vascular dilatation are frequent.
Errors in Lipid Metabolism: Disease # 5. Refsum’s Disease:
This disease occurs due to the accumulation of large amounts of phytanic acid (3, 7, 11, 15-tetramethyl hexadecanoic acid). The deficiency of the enzyme phytanic acid oxidase causes the disease.
The clinical symptoms are:
a. The early symptoms are signs of chronic polyneuropathy with distal muscular atrophy.
b. Severe pain in the knees.
c. The deep tendon reflexes are weak or absent.
d. Night blindness and narrowing of the visual fields.
e. Deafness and anosmia.
f. Cardiac involvement may lead to tachycardia.
g. The cerebrospinal fluid protein is always increased while the cell count is normal.
Errors in Lipid Metabolism: Disease # 6. Krabbe’s Disease:
This disease results in the deficiency of galactocerebrosidase which catalyses the hydrolysis of galactocerebroside to form ceramide and galactose. Galactocerebroside is the important component of myelin. The clinical manifestation of this disorder is severe mental retardation in infant.
There is nearly total absence of myelin in the central nervous system which is replaced by gliosis and ‘globoid bodies’ appear in the white matter. Diagnosis of the patients depends on the determination of the galactocerebrosidase activity in leukocytes.