Medical brain notes 25

  Inborn Errors of Metabolism   Introduction   The term inborn errors of metabolism was coined by Garrod in 1908 for four rare hereditary diseases; albinism, alkaptonuria, cysteinuria and pentosuria. Such diseases occur even during birth and thus are inherited. Inherited errors of metabolism lead to inherited diseases.   The metabolism of our body comprises two major balanced activities: anabolism (synthesis) and catabolism (degradation). Whether the metabolic changes are exergonic or endergonic, most of them have to be catalysed by enzymes. If one particular enzyme is deficient or absent then that leads to a block in the pathway of biochemical reactions leading to metabolic abnormalities which are present throughout the life and handed over to the progeny.   The absence or deficiency of an enzyme will cause an abnormal accumulation of the intermediate products of metabolism in the body and increased excretion in urine as such or their degradation products. Some...

  Galactosemia   It is an inherited disorder, in which there is inability to convert galactose to glucose in a normal manner. The incidence of this disease is about 1 in 18,000 live births.   1.  Causes   Enzyme deficiency in galactose metabolic pathway causes galactosemia. The pathway for conversion of galactose to glucose is shown in figure 7.1. In galactosemia, there is inability to metabolize galactose which may be caused by the enzyme deficiency of a = galactokinase, b = UDP Galactose 1 - phosphate uridyl transferase.   2.  Symptoms   The deficiency of galactose 1 - phosphate uridyl transferase is clinically important. Due to the enzyme defect galactose accumulates in blood and is reduced by aldose reductase in the eye to the corresponding galactitol which causes cataract.   The general condition is more severe if it is due to a defect in galactose 1 - phosphate uridyl tranferase, since galactose 1- phosphate accumulates and depletes the...

  Von - Gierke’s Disease   This is one of the groups of rare genetic disorder due to the defect in one or more of the enzymes involved in glycogen metabolism leading to excessive accumulation of glycogen in the tissue especially in liver, muscle and heart. The first glycogen storage disease identified was Von-Gierke’s disease. The frequency of this disease is one in two lakhs.   1.  Cause   This was the first inherited deficiency identified to affect liver. In this, the enzyme which is deficient is glucose 6-phosphatase that converts glycogen to glucose 6-phosphate and then to glucose.   2.  Symptoms   Both liver cells and the cells of renal convoluted tubules are loaded with glycogen. Ketosis and hyperlipidemia are also present. Glycogen content in the liver can rise to 15 per cent. Glycogen accumulates in kidney also. Massive enlargement of the liver, pronounced hypoglycemia in between meals, failure of blood glucose to rise on administration of...

  Hemophilia   The process of blood coagulation is a vital mechanism of defence against excessive loss of blood. There are nearly 13 factors involved in the mechanism of blood clotting. If any one or more of these factors are not synthesised adequately and properly that results in defect in blood clotting and thereby hemorrhage.   A number of inherited deficiency of the blood clotting factors are found in human and are collectively called as hemophilias.   Causes   Hemophilia is an inherited disease, where clotting occurs at an abnormally slow rate due to the absence of one or more of the blood clotting factors. The sufferers are known as ‘ hemophiliacs ’ or ‘ bleeders’. It is peculiar that it affects only males. The most common deficiency is that deficiency of the factor VIII, causes hemophilia A. Deficiency of factor IX causes hemophilia B. Deficiency of factor XI causes hemophilia C.   Symptoms   The characteristic findings of this disease are: · ...

  Albinism   It includes a spectrum of clinical syndromes characterized by hypomelanosis i.e., reduced synthesis of melanin pigment in skin and eyes. The defect is in the enzyme tyrosinase which is responsible for the biosynthesis of the pigment and hence the individual appears bleached. In this condition, melanin is not synthesized in the melanocytes and affects the skin, hair, sclera and choroids etc. Melanin is synthesized from tyrosine as shown in the figure 7.3. Generally, two types of albinism is seen ; a) Oculo-cutaneous albinism. In this type, there is decreased pigmentation of skin and eyes, b) Ocular albinism. In this type, there is decreased pigmentation of only eyes and not the skin.

  Alkaptonuria   This is a rare inborn error of metabolism of phenylalanine and tyrosine.   Estimated incident is 2-5 per million live births.   Cause   The disease is characterised by the deficiency of homogentisate oxidase which catalyses the conversion of tyrosine to acetyl coA and acetate. In this reaction sequence homogentisic acid (homogentisate) is an intermediate which is oxidised by the enzyme homogentisate oxidase.This results in the accumulation of homogentisic acid as shown in the figure 7.4.   Symptoms   Homogentisic acid accumulates in the tissues and blood and also appears in urine. Most striking clinical manifestation is occurrence of dark urine on standing in air. Homogentisic acid like many derivatives of tyrosine is readily oxidized to black pigments. These pigments are called as alkaptons. Urine in an exposed air slowly turns black from top to bottom.   In long standing cases, deposition of homogentisic acid derivatives in cart...

  Taysach’s Disease   Gangliosides are glycosphingolipids which are present in small amounts in the membranes of a wide variety of tissues. Nervous tissues are particularly rich in gangliosides. Generally, the carbohydrate segments of glycolipids are removed by lysosomal hydrolases in the early phases of the turn over of these compounds. Several inborn errors due to the deficiency of these hydrolases have been well documented.   Cause   Taysach’s disease is due to the absence of N-acetyl hexosaminidase A that leads to the accumulation G M2  in brain and spleen. Hence the ganglioside G M2  is called as Taysach’s ganglioside.   In this condition G M2  is not degraded to G M1  and accumulates in large amounts in lysosomes, particularly in the brain cells. The amount sometimes exceeds 100 - 300 times the normal content causing degeneration of the nervous system.   Symptoms   Muscle weakness, retardation in development and difficulty in ...

  Neoplasm   o       Cancer is the second most common cause of death in the world after cardiovascular diseases. Human of all ages develop cancer and wide variety of organs are affected.   o       Cancer cells are characterized by three properties: 1) diminished or unrestrained control of growth and cell division; 2) invasion of local tissue; and 3) spread or metastasis to other parts of the body. Cell growth and cell division are regulated by finely tuned control mechanisms.When these processes lose their control, a cell begins to grow uncontrollably. The result is the formation of a mass of cells called a tumour. The overall processes is called neoplasm.   o       The primary event in neoplasm appears to be the alteration in DNA . Most of the tumours are localized without spread and so without risk to the host, they are called benign tumours. Sometimes they start interfering with normal tiss...