The food we eat is composed of carbohydrates, proteins, and fats. After consumption, these nutrients are digested and absorbed through the intestine. Once absorbed, the bloodstream transports them to the liver, where they are further broken down into simple sugars, amino acids, and fatty acids/cholesterol.
During this breakdown process, energy is released in the form of heat, which helps maintain body temperature. The liver then uses these basic building blocks to synthesize complex sugars, proteins, and fats required for the body’s growth, repair, and development.
These complex biochemical reactions—both the breakdown and synthesis of nutrients—depend on specific enzymes. When one or more of these enzymes are absent or defective due to genetic abnormalities, the metabolic processes become incomplete or inefficient. This leads to the accumulation or deficiency of certain substances in the body, resulting in a group of conditions known as metabolic disorders.
There are hundreds of different metabolic disorders identified to date. The human body contains thousands of enzymes responsible for breaking down and re-synthesizing the nutrients we consume—proteins, sugars, and fats. These biochemical processes occur in multiple steps, and each step depends on the proper function of a specific enzyme.
If even one of these enzymes is missing or defective, the metabolic pathway becomes blocked. This can lead to the accumulation of toxic by-products or a deficiency of essential substances, resulting in damage to vital organs such as the liver, kidneys, or brain.
Therefore, metabolic disorders represent a large and diverse group of conditions—some are relatively common and well understood, while many others are extremely rare. In simple terms, the term metabolic disorder serves as an umbrella covering hundreds of individual genetic conditions, each affecting a different aspect of the body’s chemical processes.
These disorders are genetic - meaning they're passed down from parents to children through genes. It's like inheriting your parent's eye color, but instead you inherit a "broken instruction manual" for making a particular enzyme.
Some of the examples are :
ERT is most established in lysosomal storage disorders (LSDs) where the missing enzyme can be infused to reduce substrate accumulation.
Enzyme: Imiglucerase / Velaglucerase / Taliglucerase
Benefits: Improves hepatosplenomegaly, anemia, bone disease.
Enzyme: Agalsidase alfa or beta
Benefits: Reduces pain crises, stabilizes renal & cardiac function.
Enzyme: Alglucosidase alfa
Benefits: Improves cardiac hypertrophy and muscle strength; lifesaving in infantile-onset disease.
Benefits: Improved endurance, respiratory function, reduced GAG storage.
Enzyme: Sebelipase alfa
Benefits:Improve Liver enzymes,reduces dyslipidemia,slows fibrosis.
Enzyme: Cerliponase alfa (intraventricular ERT)
Benefits: Slows neurologic deterioration.
BMT helps when the donor’s hematopoietic cells produce the missing enzyme, or when disease progression involves immune or inflammatory mechanisms.
BMT is the treatment of choice if diagnosed early (2 years)
Benefits: Improves survival, preserves cognition, slows somatic disease.
BMT is effective before neurologic symptoms progress too far.
Benefits: Halts cerebral demyelination.
Benefits: Slows neuroregression if performed early.
Benefits: Preserves neurologic function only if transplanted pre-symptomatically (e.g., NBS-identified).
HSCT has been attempted historically; now largely replaced by ERT but still considered in refractory cases.
HSCT can improve survival and neurologic outcome
Think of managing a metabolic disorder like managing diabetes - it requires daily attention and special care, but children can still live happy, healthy lives with the right support and treatment.
Remember: If you have concerns about your child's growth, development, or unusual symptoms, don't hesitate to talk to your pediatrician. Early intervention makes all the difference!
| Category | Disorders |
|---|---|
| Amino Acid Metabolism Disorders |
Tyrosinemia Type 1 Maple Syrup Urine Disease (MSUD) Urea Cycle Disorders (UCDs) - OTC, CPS1, ASS1 Methylmalonic Acidemia (MMA) Propionic Acidemia (PA) |
| Carbohydrate Metabolism Disorders |
Galactosemia (GALT deficiency) Hereditary Fructose Intolerance Glycogen Storage Disease (GSD) Type I, III, IV |
| Fatty Acid Oxidation Disorders | LCHAD / VLCAD Deficiency |
| Transport / Excretion Disorders |
Wilson Disease Progressive Familial Intrahepatic Cholestasis (PFIC 1,2,3,4,5,6) Bile Acid Synthesis Defects Primary Hyperoxaluria |
| Mitochondrial / Energy Disorders |
Mitochondrial DNA Depletion Syndromes (MPV17, POLG, etc.) Pyruvate Dehydrogenase Complex Deficiency |
