Inherited ​Metabolic Disorders​

Metabolic disorders are inherited genetic conditions that result in problems with the body’s metabolism. The condition leads to an enzyme deficiency because of a defective gene. There are more than six hundred genetic metabolic disorders, all having different symptoms. Many metabolic disorders are present in the new-born period or shortly thereafter. 

Few types of Metabolic Disorders are as under.

  • Organic acidemias and amino acidopathies: This consists of a large group of disorders, which occur due to the defects in the complex biochemical pathways in the body as a result of defective function of the enzymes, cofactors or transporter protein. 
  • Lysosomal storage disorders:  Lysosomal are spaces inside the cells that break down waste products of metabolism. When toxic substances build up in the cells (due to enzyme deficiency), it can cause the following disorders:

    • ​​​Nerve damage, also known as Krabbe disease, which causes development delays in children​​

    • Bone pain, enlarged livers and low platelet counts known as Gaucher’s Disease​​

    • Hurler Syndrome, which results in abnormal bone structure and delays in development

    • Tay- Sachs disease causes progressive weakness in children which leads to death in three to four days.

  • Galactosemia: This causes jaundice, vomiting, and liver enlargement after breast or formula feeding by a new-born. It is because of the impaired breakdown of the sugar galactose. ​​
  • Maple Syrup Urine Disease: This builds up amino acids in the body which results in nerve damage and the urine smells like syrup. This is caused by deficiency of an enzyme called BCKD.
  • Phenylketonuria (PKU): This results in high levels of phenylalanine in the blood (which contribute to developmental delays in children). If the condition is not recognized, it can result in mental retardation. It is caused by deficiency of the enzyme PAH.
  • Mitochondrial Disorders: Problems inside mitochondria (the powerhouses of cells), which comprises of a heterogeneous group of disorders, which often have multi-system involvement. Defective functions of the mitochondria leads to damages of organs, which are high energy dependents including the muscles, brain, eyes and heart. However, any organ of the body can be involved.
  • ​Metal Metabolism Disorders: Levels of trace metals in the blood are controlled by special proteins in the form of enzymes and transporter proteins.​
​​

Symptoms of Metabolic Disorders are disease specific and can vary remarkably. Few are listed below:​

  • ​Inborn Metabolic Disorders (presenting with coma)

When a defective gene causes an enzyme deficiency inborn errors of metabolism (IEM) occur. They can present with variable presentations:

    • ​Low blood sugar, presence of acids in blood (metabolic acidosis or lactic acidosis), presence of acids in urine (ketonuria), high ammonia (hyperammonemia)

    • Lethargy, Poor appetite, Vomiting, Weight loss, Jaundice, Seizures, Coma, progressive enlargement of liver/spleen

    • Abnormal odour of urine, breath, sweat, or saliva

  • Neuro-metabolic Disorder

    • ​Intractable seizures, Muscle pain,  

    • Developmental delay or mental retardation

    • Neuroregression seen in children who were previously normal.

  • Seizures not responding to usual anti-convulsants

    • such seizures can be identified early in their presentation, after failure of two antiseizure drug trials

  • Storage Disorders

    • ​Progressive enlargement of liver/spleen, which may occur in presence or absence of developmental delay or neuroregression.

    • Low blood sugar, low blood sodium, hyperosmolar non-ketotic hyperglycemia, high blood sodium, low blood calcium and high blood urea.

  • Metabolic Cardiomyopathy

    • ​Impaired myocardial functions either Dilated Cardiomyopathy or Hypertrophic Cardiomyopathy can be seen in IEM. Most IEM related cardiomyopathies are treatable and reversible.

  • Metabolic Liver Diseases​

    • ​Enlarged liver with or without impaired liver functions (LFTs) can be due to a number of IEM.

  • Pre-natal Genetic Counselling

    • ​Couples with multiple miscarriages, stillbirths, or babies born with suspected genetic disorders, so that they may receive guidance in diagnosis, suggestions in additional testing and referrals if warranted. Help in directing medical care, and provide counselling for affected patients and their families​


These disorders are usually present at birth and our doctors at the Children’s Hospital Service Line at The Aga Khan University Hospital will be able to diagnose them at birth.​
Your time with your doctor maybe limited, so make sure to prepare for your visit beforehand. Here are some tips to help get you started.​
Our doctors at the Children’s Hospital Services at The Aga Khan University Hospital will be able to diagnose these disorders at birth. If not at birth, they may come to the forefront in usual monthly screenings by your paediatrician. If it doesn’t show at the birth of your child, these are only then diagnosed when symptoms appear. Many screenings, DNA tests and blood tests are available to highlight these problems in your child.

The doctor may recommend the below tests:
  • ​Urine Organic Acid
  • Plasma Amino Acid
  • CSF Amino ACid
  • Uribe Amino Acid
  • Urine Succinylacetone
  • MSUD Profile
  • Methionine Homocysteine Profile
  • Plasma MMA
  • Urine Orotic Acid​

Very limited treatments are available for this disorder. The current technology worldwide cannot fix the genetic defect; however, it can work around metabolism. Treatment follows simple principles:

  • Intake of food needs to be such that it supports the metabolic problem​.

  • Avoid food items that obstruct metabolism.

  • Remove or reduce intake of drug or foods that do not metabolize properly

  • Intake of chemicals that are non-present in the metabolism

Treatment may also include measures such as:

  • Special diets that do not hold certain nutrients

  • enzyme replacements or supplements that support metabolism

  • Chemical treatment of blood to detoxify dangerous metabolic by-products​​


The Aga Khan University Hospital offers various support services to help with managing or recovering from the disease or condition. These include but are not limited to nutrition, physiotherapy, rehabilitation, specialized clinics and some patient support groups. Your doctor or nurse will advise you accordingly.

The Aga Khan University Hospital offers financial assistance to those who are in need and fulfil the eligibility criteria. For further information, you can contact the Patient Welfare Department. You can find the contact number of the Patient Welfare Department in the ‘Important Numbers’ section on the website homepage.​

The financial counselling staff is available during office hours, at the main PBSD (Patient Business Services Department), to answer your financial queries on treatments’ costs and authorize admissions on partial deposit as per hospital policies allow. The financial counsellor in the emergency room is open 24/7. You can find the contact number of the Patient Business Services in the ‘Important Numbers’ section on the website homepage.​


Your doctor and or nurse will give you specific instructions about the prescribed medication. Please ensure that you take or use the prescribed medicine as advised. It can be dangerous to your health if you self-prescribe. Please inform the doctor or nurse beforehand if you have experienced any adverse reactions to any medications in the past. If you experience any symptoms of drug poisoning, overdose or severe reaction please contact the Pharmacy Service at The Aga Khan University Hospital immediately. You can find the contact number of the Pharmacy Services in the 'Important Numbers' section on the website homepage.​

​


 


 

The information provided on our website is for educational purposes and not intended to be a substitute for medical advice, diagnosis or treatment. You should always seek the advice of your doctor or other healthcare professional provider.