Metabolic Disorder in Children

Metabolic disorders in children: What is it?

Our food consists of various carbohydrates, proteins and fats.  When we consume them they get digested in stomach and get absorbed from intestine. From intestine, blood carries these particles into liver.  They are further broken down to simple sugars, aminoacids and fatty acids/ cholesterol. During the breaking process energy is created in the form of heat (this is how body is warm). Using these basic particles of simple sugars, aminoacids and fatty acids/ cholesterol, the liver cells manufacture complex sugars, proteins and fats necessary for growth and development of our body.  For breaking and re synthesising our body depends on enzymes. In the absence of enzymes, the process of breaking and re synthesising is defective and not complete resulting in diseases, called metabolic disorder.

How many metabolic disorders are there?
There are more than 100 types of proteins, sugars and fats and there are 100s steps involved in gradual breakdown to re-synthesis. So there are 1000s of enzymes in the body. Absence of any one enzyme would lead on to block in the pathway resulting accumulation of toxic by products which could damage liver, kidney, brain etc. So there are hundreds of metabolic disorders of which some are very common and some are very rare. In simple terms, metabolic disorder is a broader term, which encompass hundreds of specific disorders.

Could you give a simple example?
When protein is broken down ammonia is produced, this ammonia is very toxic to brain cells and liver convert this ammonia to urea, which is easily excreted in urine. This process of converting ammonia to urea is called urea cycle and has five steps mediated by 5 enzymes. Absence of even one of the enzyme, could lead to increased ammonia in body, which will affect brain cells and eventually cause death.

What is the clinical manifestation of metabolic disorders?
They can manifest in various ways. Affected patients can have low blood sugars, jaundice, renal failure, liver failure, fits, behavioural changes, sometimes coma and death.

When do they manifest disease?
The metabolic disease manifest only when they eat the specific sugar, protein or fat, for which they lack enzymes to digest. Sometimes, other metabolic pathways could compensate or remove the toxins and the disease manifests only during periods of stress like prolonged fasting or infection.

Why it affects children more?
Children are born with the disease as it is hereditary condition, but manifestation happens only when that specific food component is introduced. So potentially the disease manifestation can happen at any age. For example there is a disorder called Hereditary Fructose Intolerance, where the patient cannot digest fructose (type of sugar found in fruits and vegetables). So disease manifests at diarrhoea or liver failure, only when fruit and vegetables are introduced in to their diet. This usually happens around 7 or 8 months, when parents introduce fruits to baby.

How common is metabolic disease?
The incidence of disease varies from 1 in 2500 to 1 in several million. Few disorders are so rare that, only four of five cases have been reported worldwide.

I am scared whether my child has got it, when should I think about it?
There are few signs and symptoms that suggest underlying metabolic disorders. Frequent low blood sugar levels leading on to fits, delayed developmental milestones, jaundice, enlarged liver or spleen, generalised muscle weakness (hypotonia) are few of common symptoms related to metabolic disorder.

Can it be prevented?
Usually they are hereditary disorders, where both mother and father pass on the genes. We call them carriers as they have one defective gene and one normal gene and don’t manifest disease. When they have a child there is one in four chance that the defective genes could come together and cause disease (in theory one in four children are affected if both parents are carriers). This is why doctors discourage marriage with in relatives.

Can it be diagnosed immediately after birth?
There are screening test available for common metabolic disorders, usually it requires only a drop of blood on filter paper from newborn baby. Number of metabolic tests carried out varies from country to country, depending on common metabolic disorders present in the country.

How it could be treated?
Dietetic management forms the basis of treatment. Exclusion of the specific sugar, protein or fat is the only treatment. As children needs all the three components in their diet for growth, it is very difficult to manage. There are special feeds available in the market but still it might be difficult to eliminate certain food components. There are certain medicines, which will help eliminate the toxins from body, but they work only partially.

Once diagnosed can it be cured?
It depends on where the enzyme is present predominantly. Most of the enzymes are present predominantly in liver and liver transplantation offers cure to many metabolic conditions. If the enzymes deficiency is all over the body, no effective treatment is available, apart from dietetic restriction.

What’s the future?                                     
Research is underway to develop the missing enzymes so that it could be injected (like insulin), but there is a long way to go.