Which body tissues can be damaged by severe inherited metabolic disorders?

Severe inherited metabolic disorders can cause damage to virtually any tissue in the body, as metabolic pathways are fundamental to cellular function throughout the organism. The specific tissues affected depend on the nature of the enzyme deficiency and the resulting accumulation of toxic substrates or the lack of essential products.123

Commonly affected areas include:

• Brain and Central Nervous System: Damage to the developing brain is a frequent and characteristic consequence of severe metabolic disorders, often manifesting as encephalopathy, intellectual disability, or neurological impairment.123
• Liver and Spleen: Many disorders, particularly those involving glycogen or lysosomal storage, lead to the enlargement of these organs due to the accumulation of undegraded macromolecules.43
• Muscles: Defects in metabolic pathways, such as those involved in glycogen degradation, can impair muscle function and lead to weakness or other muscular symptoms.14
• Bones: Certain storage disorders are associated with skeletal abnormalities and bone disease.3
• Peripheral Tissues: Depending on the specific condition, other systemic organs and peripheral tissues may also be damaged.3

The severity of tissue involvement often correlates with the degree of enzymatic dysfunction.53