Dr Ng Min Ching
General Practitioner

A vast number of processes are occurring in the human body at any one time. Living material is being built and broken down all the time from proteins, fats, carbohydrates, enzymes, hormones and other molecules.

These processes begin with the fertilisation of the egg by the sperm and continue through growth, maturation, ageing and death of an individual. Metabolic diseases are the result of one or some of these processes going awry.

However, one faulty reaction does not automatically manifest itself as an illness as compensatory mechanisms can help to rectify the error. Consequently, most errors are amended before any damage is generated. It is only when the body is unable to correct the mistake caused by a critical enzyme or step that a disease is produced. Metabolic diseases encompass a wide range of disorders. It ranges from the common obesity and diabetes to the rarer phenylketonuria.

The dangers of metabolic diseases
On one end of the spectrum, there is very mild biological abnormality with no obvious clinical signs and symptoms. The affected individual looks and feels normal. At the other end of the spectrum, deformities, fits, mental retardation, psychosis, organ failure and death can occur.

Types of metabolic diseases:

• diabetes mellitus

• obesity

• gout

• inherited and storage disorders of protein, fat and carbohydrate metabolisms

• inherited defects of membrane transport

• iron storage disorder, copper excretion disorder

• porphyria

• glycogen, mucopolysaccharide and lysosomal storage diseases

• inherited disorders of connective tissue

• blood disorders e.g. thalassaemia, haemophilia, and G6PD deficiency.

Here we discuss some of the more common metabolic disorders.

Diabetes Mellitus. It is the sixth leading cause of death in Singapore and the commonest of the serious metabolic disorders. The word diabetes means excessive urination. The illness is characterised by having too much sugar in the blood. In this condition, too little insulin (a hormone that controls the storage and release of sugar from body cells) is produced and/or the body fails to respond to the insulin. The patient passes urine frequently, feels thirsty as a result and drinks plenty of water. There is lethargy and weight loss. Failure to receive appropriate treatment will lead to complications like stroke, heart disease, kidney and eye damage, gangrene or even death.

Obesity. Obesity is a major risk factor for diabetes, heart disease, high blood pressure, stroke and sleep apnoea. It occurs when the caloric intake exceeds the caloric expenditure. The causes are multifactorial: socio-economic, metabolic and inherited. As society becomes more affluent and lifestyle grows more sedentary, the incidence of obesity increases. One way of defining obesity is by using the body mass index (BMI).

BMI = Weight in kg divided by the square of height in metres
BMI 20-25 => normal
<20 => underweight
>25 => obese

Recent studies have suggested that a protein known as leptin helps in body regulation of fat. Generally, obese people produce more leptin compared to thinner ones. In the future, leptin therapy may be an important drug in the management of obesity.

Gout. Gout mainly affects men. In this disorder, there is a higher than normal amount of uric acid in the body. The excess uric acid is deposited in and damages the joints, soft tissue, kidneys and bladder. Alcohol consumption and a diet rich in purines (e.g. red meat, organ food, ikan bilis) aggravate the disease.

G6PD Deficiency. Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common condition in South East Asia. It affects only the males. Babies born in Singapore are routinely screened at birth for the lack of this enzyme. Patients develop jaundice and anaemia upon exposure to mothballs, fava beans, specific drugs and during acute illnesses.

Thalassaemia. In this inherited disease, the red blood cells are abnormal and easily damaged. In extreme cases, the child is either stillborn or suffers from severe anaemia, repeated infections and failure to thrive.

Prevention and treatment
Genetic screening is useful in diseases with an obvious pattern of genetic inheritance. It has two important functions - one, for early identification of an individual at risk before the condition develops or worsens; two, to identify couples at risk so that they can benefit from genetic counselling prior to having children.

In beta thalassaemia, parents who are both thalassaemia carriers have a 25 percent chance of having a normal child, 50 percent chance of having one with severe thalassaemia and 25 percent chance of having one who is also a carrier. However, if only one parent is a carrier, the child has a 50 percent chance of being normal or a carrier. Undergoing pre-marital genetic counselling will enable the couple to have a better understanding of themselves and prepare them for married life.

Today, many inherited diseases can be identified by the analysis of amniotic fluid and cells or by the examination of foetal blood while the foetus is still in the mother's womb

Since metabolic disorders can be precipitated or aggravated by environmental factors, lifestyle and dietary modifications are important in the prevention or treatment of these illnesses. Some examples are:

• proper exercise and avoidance of excessive food intake in obesity

• appropriate diet in diabetics

• avoiding a diet rich in purine in gout

• a low phenyalanine diet in phenylketonurics

• staying away from mothballs, certain food and drugs in people with G6PD deficiency.

Treatment is directed towards the underlying cause of the disease. The treatment modalities are:

• Lifestyle modifications (as mentioned above).

• Drugs.
  (i) Replacement of the deficient substance e.g. giving insulin to diabetic patients who cannot produce enough of it.
  (ii) Removing the aggravating agent e.g. medication to decrease the amount of uric acid in the body in gout.

• Surgery. Bone marrow transplants are useful in severe thalassaemia. In advanced cases of gout, stones form in the kidney, where the stones have to be removed surgically. When kidney or liver failure has occurred, the respective organ transplants can be performed.

References:

1. Braunwald, Isselbacher, Petersdorf, Wilson, Martin and Fauci. Harrison's Principles of Internal Medicine, 11th edition. (1987). MacGraw-Hill Book Company, New York, U.S.A.
2. Rockefeller Institute for Medical Research, www.rockefeller.edu/pubinfo/leptinlevel.nr.html

Date reviewed:  February 2005