Mozamila Mughal
What are Inborn Errors of Metabolism (IEM)
Inborn errors of metabolism(IEM) are genetic defects, which are rare in the human body. What happens? The body cannot convert energy from food due to missing enzymes; enzymes are special proteins that act like a key to open up the food product to extract proteins, fats, and carbohydrates for utilizations in body for growth and repair. When a food product is not broken down in body its toxic waste builds up and causes large number of symptoms that leads to developmental delay, disability, and even death of children.
Why Does a child have these genetic defects of IEM?
IEM are inherited defects, meaning they are present at birth. The affected child inherits the defected gene from both parents. Parents are healthy because they have one working copy of the defective gene in their body, but the child gets both defected copies. There is a 25% chance with each pregnancy that either a child would be having full defect,become a partial carrier, or no defect .Some types of defects affect only boys in this inheritance pattern.
What are Signs and Symptoms of IEM
When an infant is born, within 24 hours, feeding is started either with mother feed or formula feed. As soon as food enters the digestive system, due to absence of missing enzymes, proper breakdown of the feed does not take place, leading to the buildup of toxic waste in body . Infants start to have nausea, vomiting, low sugar in blood, and if this continues it leads to unconsciousness, seizures, and if left untreated it can lead to disability or death. Patient should be rushed to hospital, where appropriate tests are done.
What Lab Tests are Done to Diagnose IEM
In Pakistan, some disorders are picked up by urine and plasma proteins tests, while certain disorders require more sophisticated tests like genetic testing, which is not available in Pakistan.
What is Treatment of IEM
Once the nature of the defect is diagnosed, various types of treatments are done to manage these defects lifelong:
Medicine to control the toxic waste in the body.
Diet restriction from offending food.
Special formulas designed to eliminate the offending nutrient.
Vitamin supplementation.
Liver or kidney transplant.
Bone marrow transplant.
How to Prevent IEM
Newborn screening within 24 to 48 hours of birth before child gets sick and complications start. It requires 3-4 drops of blood on a special paper to screen large number of defects.
Public awareness about IEM defects.
Genetic counseling to prevent cousin marriages among families known to carry the defect.
IEM Situation in Pakistan
1- Non-Availability of Newborn Screening
There is no newborn screening in Pakistan.The prevalence of any condition depends on proper screening and registry of disorders,but due to a high rate of cousin marriages in Pakistani culture, there is a high incidence of patients in almost all categories with organic acidemias, urea cycle defects, fatty acid oxidation disorders, carbohydrate defects, and even cases of some rare disorders which are reported in fewer numbers in the world, that are present in Pakistan. This leads to the assumption that we are sitting on an iceberg without knowing the actual depth of the problem.
2- Cousin Marriages
As per data shared by a German genetic testing lab in 2020, Pakistan has a 73% cousin marriage rate with the largest community of deaf children. People suffering from genetic diseases in the country are estimated between 14-16 million while 1.6 million mutations have been found in Pakistan.
3- Lack of Awareness Among Health Care Providers
Due to a lack of awareness and monitoring at the grass root level, there are no guidelines in tertiary and secondary care hospitals when patient turns up in emergency. 80-90% of tests done are unnecessary and waste meager resources of the patient’s family, instead, they could be better directed for genetic testing with definite direction to follow results of test.
4- Lack of Support from
Government
Since there is total absence of recognition about this problem in the health sector, this reflects on Governmental lack of support. In 2020 – 2021, some provision was made in the Baitul Maal, Sindh to start monthly support to parents in acquiring special formulas, but this initiative went on the back burner after one year.
5- Expensive Special Formulas
Children identified with defects are started on special metabolic formulas, which do not contain offending nutrients. Metabolic formulas are imported by international companies operating in Pakistan. With ever fluctuating dollar rates, these formulas end up being highly expensive,with prices starting from Rs 6,000 to Rs 22000 per tin. Children need at least 3-4 tins per month from 0-6months of age and after 6 months at least 2 tins per month and need life long support of theses formulas to survive .This expense is nearly impossible in current economic conditions, resulting in inability to provide vital support for growth and development.
6- Comparison with Metabolic Formulas in India
India has been able to achieve self-sufficiency in IEM formula production within country, this reduces the cost of import and subsequent taxes due to exchange rates. For example, if Glutaric acid type 1 formula 400gms for children under age of 1 year is available by an imported brand in Pakistan, priced at RS 9,771, the same formula in India is costing 986 Indian rupees for a 400gms gram tin.
7- Non–Availability of Vital Medications
If a child is diagnosed accurately through genetic testing, and the type of disorder requires any special medication along with metabolic formula, it is highly possible that the child will be disabled or expire waiting for medication. So, often, the real dilemma starts after the diagnosis is made, as care provider is stuck with the patient whose treatment is possible but cannot be made available in Pakistan.
Author worked as
Consultant Nutritionist at Shifaam Epilepsy Clinics
Karachi, IEM Metabolic Trained Emory University USA, EX HOD, Clinical
Nutrition AKUH Karachi