INBORN ERRORS OF METABOLISM AND HOMOEOPATHY
H/Dr.Mirza Saleem Baig (Gold Medallist)
President: Pakistan Homoeopathic Research Council (PHRC)
Definition;
Inborn Errors of Metabolism, a term coined by Sir Archibald Garrod over approx. 55 years ago. They are important, because they demonstrate how one simple biochemical error can effect many tissues and often produce severe disease. If they are diagnosed early enough, successful treatment may be instituted.
Sometime genetic error results in the complete failure to form a protein, e.g. an albuminaemia. In many instances the protein formed as a result of gene action is an enzyme. The concept one gene, one enzyme is useful when one considers the conditions characterised by the presence of a defective enzyme. An example of this is the abnormal pseudocholinesterase, which may be found in plasma of certain individuals who in all other respects appear to be normal. These people are unduly susceptible to the action of short acting muscle relaxant drugs.
When a structural gene is involved there can be one of several effects. The protein formed in the body, being of abnormal composition, may differ in chemical or physical properties. The many variants of hemoglobin are example of this. In the case of enzymes, their specific activity may be lessened or their stability altered. It should be noted that it is technically difficult to distinguish between three possibilities.
Diseases Caused By Inborn Error of Metabolism;
Galactosaemia;
This is condition in babies who fail to thrive, have large livers and pass galactose, amino acid and albumin in urine. Mental retardation, catract, and cirrhosis of liver ultimately develop. The defect is due to usually to an absence of the enzyme galactose 1-Phosphate to glucose. It follows that galactose (from the lactose of milk) cannot be utilised it accumulates and is excreted in the urine. Galactose itself is not toxic but galactose 1-Phosphate probably interferes with some metabolic process (possibly involving phosphoglucomutase, which converts glucose 1-Phosphate to glucose 6-Phosphate) which is essential for the proper development of the brain, lens, liver and kidney. The accumulation of the sugar alcohol galactiol formed from galactose in the lens has been suggested as the cause of the cataracts. The avoidance of galactose in the diet from an early age may prevent the baneful effect of this abnormality.
A mild form of galactosaemia, with cataract development in childhood as its major symptoms has also been described. It is due to a deficiency of galactokinase.
Alcaptonuria (alkaptonuria);
In this condition the urine contains large amounts of homogentisic acid, which cause it to darken on standing if the reaction is alkaline. Staining of the diapers may be the first sign of the disease. The condition is of little consequence except that as the patient grows older, his cartilages and ligaments become pigmented (ochronosis) Osteoarthritis may develop, the reason for which is not known. Alcaptonurics are unable to metabolise homogentisic acid, which is an intermediary in the metabolic breakdown pathway of tyrosine and phenylalanine. There are however, alternative metabolic pathways, which probably explain why no serious develops. Alcaptonuri was the first human disorder found to be inherited as a Mendelian autosomal recessive characteristic and the study of this condition led Garrod to formulate the concept of enzyme deficiency as a cause of disease.
Phenylketonuria;
Between 3 and 5 persons per 100,000 of the population exhibit this condition which commences shortly after birth and is characterised by retardation of mental development. Other neurological abnormalities, hypopigmentation of the skin and some time eczema also occur.
In the classical form of the defect there is an absence of the hepatic enzyme phenylalanine hydroxylas, which is normally, converts into tyrosine that dietary phenyalanine not utilised in the synthesis of protein. Therefore the level of phenyalanine in the blood (normally up to 2mg/dl) and cerebrospinal fluid is high. The urine contains, in addition to phenyalanine phenylpyruvic acid, which gives a green colour with ferric chloride solution. If the disease is detected early, certainly before the age of six months, and the patient given a diet low in phenyalanine content, brain damage can be largely averted. The administration of tyrosine itself dose not prevents the development of mental deterioration, so presumably phenyalanine or one of its derivatives is toxic. The condition is inherited as an autosomal recessive trait; 1% of the population are heterozygotes, and can be detected by the administration of a dose of phenyalanine, when the blood levels rise. The dose not occurs in a normal individual.
Lesch-Nyhan Syndrome;
This is inherited as a sex-linked recessive trait and is characterised by hyperuricaemia, gout, mental deficiency, and spastic paralysis with choreoathetosis. Its most remarkable characteristic is impulsive, uncontrollable self-mutilation of the fingers and lips. This bizarre behavior may result in great tissue loss, and yet at autopsy no neurological structural abnormality can be found. These patients lack the enzyme hypoxanthine; guanine phosporibosy Itransferase used in the synthesis of nucleotides. In its absence there is an overproduction of uric acid. The enzyme defect can be demonstrated in cells cultured from the patient and also in some individuals who suffer from gout only. The relationship between the enzyme defect and other features of the Lesch-Nyhan syndrome is not understood. The disease is of great interest because of the association of a known biochemical lesion with a specific, aggressive, destructive type of behavior, itself a gross caricature of the type of behavior that afflicts the human being today.
Glucose 6-Phosphate Dehydrogenase Deficiency;
Patients lacking this enzyme in their red cells are liable to develop acute heamolytic crises if they take certain drugs, e.g. primaquine, sulphones and sulponamides.
A large number of variants of glucose 6-phosphate dehydrogenase deficiency are now known. The enzyme is necessary for the conversion of glucose 6-Phosphate to 6-phosphogluconate in the hexose monophosphate shunt. On this depends the maintenance of glutathione in the reduced state in the red cell. For reasons, which are not clearly understood, reduced glutathione is required for the maintenance of the integrity of the red-cell membrane particularly under the influence of certain drugs.
Glycogen Storage Diseases (glycogenoses):
There are a number of inherited disorders in which there is an excessive accumulation of glycogen in various tissues due to an abnormality of glucose metabolism. These may be divided into eight main groups according to the enzyme defect.
1-Glycogen-Storage disease;
This is inherited as an autosomal recessive trait, and is due to glucose 6-Phosphate deficiency. The liver normally retains about 60% of the glucose absorbed from a carbohydrate meal; it is phosphorydrate to glucose 6-Phosphate and subsequently stored as glycogen. Hours later this glycogen is broken down again to glucose 6-Phosphate and subsequently free glucose is released into the blood stream to maintain the blood glucose level. In the absence of glucose 6-Phosphate is not broken down, glucose is not released, and hypoglycemia result. In this way a normal type of glycogen is retained in the liver and to a lesser extent the kidneys. Fat is metabolised for energy requirements (as in diabetes mellitus) and hyperlipoproteinaemia and ketosis develop. Furthermore, the accumulated glucose 6-Phosphate is deposed of by increasing anaerobic glycolysis. Lactic acid and Pyruvic acid accumulate, thereby accentuating the acidosis. Hyperuricaemia is not uncommon and appears to be due to impaired renal excretion of uric acid. It is suggested that competitive inhibition occur by lactate excretion.
This disease shown itself in infancy, enormous, hepatomegaly is being the most prominent feature. The kidneys are also enlarged. Hypoglycaemic fits are common but as the child grows these becomes less frequent. The chronic acidaemia appears to be responsible for the stunted growth and the osteoporosis that these children exhibit. There is a high incidence of cutaneous xanthomata and gouty tophi, from which the xanthomata must be distinguished.
2-Glycogen-Storage disease;
This is inherited as an autosomal recessiver trait, and is due to a deficiency of the lysosomal enzyme. The disease is generally detected at about 2 months of age, and characterised by pronounced hypotonia and enormous cardiomegaly. The child usually dies by about the age of 2 Years.
There is increased amount of normal glycogen deposited in the heart, tongue, and other skeletal muscles. This disease can be regarded as a type of lysosomal disease. The biochemical defect is a deficiency.
3-Glycogen-Storage disease;
Clinically this resembles the type-I disease, but is less sever. There may be splenomegaly, and hepatic enlargement tends to diminish at the age of puberty. Gout does not occur in this type of disease.
The disease is inherited as autosomal recessive trait, and is due to a defect in the debarnching enzyme in the absence of which glycogen cannot be broken down completely. The tissues accumulate an abnormal form of glycogen, which resembles the limit dextrin that is produced by the degeneration of glycogen by phosphorylase in the absence of the debranching enzyme.
4-Glycogen-Storage disease;
This rare condition is characterised by failure to thrive, progressive hepatic cirrhosis, and death within the first two years of life. An abnormal, less soluble form of glycogen is laid down in the tissue due to a deficiency of the branching enzyme.
5-Glycogen-Storage disease;
In this uncommon disease there is an inability to perform strenuous exercise because of the development of cramps. Myoglobinuria occurs in about half the patient. These symptoms generally commence between the ages of 20 and 40 years, and are later followed by muscular wasting and weakness. The defect is in the muscle phosphylase, an enzyme that is essential for sustained, vigorous exercise.
6-Glycogen-Storage disease;
This is described as resembling the type-I disease but being much milder. Some cases have been reported as having a low liver phosphorylase activity, but the condition is probably a heterogeneous group of different disease temporarily assembled together pending their further classification.
7-Glycogen-Storage disease;
This is very rare condition resembles the type-V disease. It is due to a deficiency of muscle phosphofructokinase, and glycogen accumulates in many muscles.
8-Glycogen-Storage disease;
In this condition there is a deficiency of hepatic phosphorylass b kinase, an enzyme required to activate phosphorylass. Since the phosphorylass is itself normal, the disease has now been removed from type VI and placed in this separate group.
Clinically the disease is mild, being characterised by mild hypoglycaemia and hepatomegaly due to glycogen deposition. It is inherited as an X-linked trait, and is fully manifest only in males.
Lysosomal Enzyme Defect;
The concept of lysosomal storage disease, proposed by Hers in 1965, embodies the notion that because a specific lysosomal enzyme is absent; its natural substrate will accumulate in the cell. This emphasises the fact that lysosomes normally play a vital part in the removal of effect cytoplasmic components. Although rare, these diseases are of great interest because they illustrate how a simple enzyme defect can have devastating effect. Many of the disease can be detected in utrero by cultruing fetal cell and demonstrating the defective or absent enzyme.
Mucopolysaccharidoss.
A careful study of these diseases has shown remarkable genetic heterogeneity. Thus although most patients with Type 2 glycogenosis die within a few months of birth, a few have mild symptoms and live for years. Likewise the characteristic cherry red spot at the macula in-patient with Tay-Sachs disease is also present in the gangliosidoses and in Niemann-Pick disease, although in these conditions the enzyme defect is different.
Homoeopathic Treatment;
Homoeopathy has a vast range of medicine for metabolic disorders. But there is we are going to discuss about some medicine of metabolic disorders.
Iodum (Iodine);
Rapid metabolism, metabolic disorders. Hungry with much thirst betters after eating. Enlarged lymphatic glands tubercular type. All glandular structure respiratory organs, circulatory system are especially affected, atrophy. Iodine arouses the defensive apparatus of the system by assembling the mononuclear leucocytes whose phagocytic action is marked, at a given point. Arthritis deformans. Act prominently on connective tissue. Goiter and nutritive disturbances are the pathological condition at the basis of its symptomatology. Sluggish vital reaction, hance chronicity in many of its espects. Tendency of ulceration. Liver and spleen sore and enlarged. Jaundice mesenteric glands enlarged. Pancreatic disease. Myocarditis, Tachycardia. Joints inflamed and painful. Gonorrheal rheumatism. Rheumatism of nape and upper extremities. Rheumatic pains nightly pains in joints.
Natrum Carbonicum (Carbonate of sodium);
All the Natrums stimulate cellular activity and increase oxidation and metabolism. Anaemic, very weak ankles are all peculiar Natrum carbonicum conditions. Unable to think. Mental weakness and depression. Very weak digestion caused by slightest error of diet. Old despeptics. Great weakness of limbs, especially in morning. Soreness between toes and fingers. Inclination to perspire easily, or dry rough, cracked skin.
Natrum Muriaticum (Chloride of Sodium);
The prolonged taking of excessive salt causes profound nutritive changes to take place in the system. An alteration in the blood is causing a condition of anaemia and leucocytosis. There seems also to be retention in the issue of effect materials giving rise to symptoms loosely described as gouty or rheumatic gout. Hyperthyroidism, Goiter. Addison’s disease, Diabetes. Depressed, particularly in chronic diseases. Anaemic headache of schoolgirls. Eyes muscles weak and stiff letter run together. Sees spark. Asthenopia due to insufficiency of internal recti muscles. Cataract incipient. Numbness, tingling of tangue. Palms hot and perspiring. Arms and legs, but especially knees feel weak. Dryness and cracking about finger nails. Ankles weak and turn easily. Urticaria itch and burn. Eczema raw, red, and inflamed. Alopceia.
Natrum Salicylicum (Salicylate of Sodium);
Has an extensive range of action affecting the head, ear, throat, kidneys and liver and on metabolism. Increases the quantity of bile. Follicular tonsillitis. Albuminuric retinitis with heamorrhage. Defines. Oedema, Urticaria red in circumscribed patches. In acute articular rheumatism lambago, sciatica.
Phosphorus (Phosphorus);
Phosphorus irritates, inflames and degenerates mucous membranes, irritates and inflames serous membrane, inflame spinal cord and nerves, causing paralysis. Disorganizes the blood, haematogenous jaundice. Produces a picture of destructive metabolism. Causes yellow atrophy of the liver and sub acute hepatitis. Great susceptibility to external impression. Polycythaemia. Blood extravasation fatty degeneration’s, cirrhosis, caries, are pathological states often calling for phosphorus. Muscular pseudo-hypertrophy, neuritis. Scurvy. Pseudo-hypertrophic paralysis. Osteo myelitis. Loss of memory. Paralysis of the insane. Neuralgia, itching of scalp dandruff, falling out of hair in large bunches. Cataract, black points seem to float before the eyes. Letter appears red atrophy of optic nerve. Glaucoma, thrombosis of retinal vessels and degenerative changes in retinal cells. Hearing difficulty. Liver congested. Acute hepatitis. Fatty degeneration jaundice and pancreatic disease. Weak spine Arms and hands becomes numb. Joints suddenly give way. Fungous hematodes and excrescence’s.
X-Ray (Vial containing alcohol exposed to X-Ray);
Repeated exposure to Roentgen (X-Ray) has produced skin lesions often followed by cancer. Distressing pain. Changes take place in the blood lymphatics and bone marrow. Aneamia and leukaemia. Has the property of stimulating cellular metabolism. Arouses the reactive vitality, mentally and physically.