Enzyme Deficiencies vs. Structural Protein Abnormalities

• Focus of learning objective 7 is understanding differences between disorders caused by enzyme deficiencies and those caused by abnormalities in structural proteins or tumor suppressor genes
• The objective emphasizes understanding the differences between disorders caused by enzyme deficiencies and those caused by abnormalities in structural proteins

Key Characteristics

• Highlights shared characteristics between disorders
• Utilizes a table to showcase enzymatic deficiency disorders, including relevant genes
• Pathology of some diseases covered in other objectives

Memorization

• Memorizing the table is not required for the test
• Memorize genetic symbols or gene names if specifically covered in relation to disease pathology
• Focus on genes covered specifically in relation to the disease's pathology
• Ehlers-Danlos syndrome is linked to many genes, so memorizing them all would be too difficult

Enzyme Deficiency

• Most enzyme disorders are inborn errors of metabolism
• Mutated enzymes lead to buildup of toxic products or prevent proper transport of metabolites
• Some disorders are transport disorders, which involve the inability to move substances across cell membranes
• Cystic fibrosis is a transport disorder where chloride ions are not properly transported across cells

Abnormalities in Structural Proteins

• Structural proteins maintain integrity of tissues, while tumor suppressor genes prevent uncontrolled cell division
• Marfan syndrome involves a mutation in the fibrillin-1 gene, a structural protein for connective tissue integrity
• Most disorders affect the structural function of tissues rather than metabolism or transport

Inheritance of Enzyme Disorders

• Most enzyme-related diseases are autosomal recessive.
• Autosomal recessive means an individual must inherit two defective copies of the gene for the disease to manifest
• Individuals typically have two copies of the DNA coding for the enzyme; if only one copy is functional, the disease may still present.
• Tay-Sachs disease is an autosomal recessive disorder caused by mutations in the HEXA gene.
• Conditions like Hunter syndrome may present even if just one copy is functional
• Familial Hypercholesterolemia is autosomal dominant
• Autosomal dominant means only one mutated copy of the gene is needed for the disease to manifest
• Diseases related to enzymes in metabolism are generally autosomal recessive because a single functional enzyme is usually sufficient for normal metabolism

Inheritance of Structural Proteins

• Mutations in one copy of the gene will reduce protein level, leading to haploinsufficiency
• Haploinsufficiency occurs when one functional copy of the gene does not produce enough of the protein to meet the body’s needs
• Example, Osteogenesis imperfecta, or OI, caused by mutations in COL1A1 or COL1A2 genes, leads to brittle bones due to reduced collagen production

Vignettes for Inheritance

• The following scenarios describe genetic predispositions

Disease Related to Acetylburnic Acid Metabolism

• Father's brother has a disease caused by an inability to metabolize acetylburnic acid
• Most likely inheritance: Autosomal recessive
• Indicates a metabolic block causing the buildup of a metabolite, which is typical of autosomal recessive disorders

Triple Negative Breast Cancer

• Multiple female family members diagnosed with triple-negative breast cancer
• Most likely inheritance: Autosomal dominant
• Suggests a genetic predisposition passed down through the family, as multiple relatives are affected

Salt Transport Deficiency

• Mother's disease involves an inability to transport salts
• The most likely inheritance is autosomal recessive
• Diseases affecting ion transport, such as cystic fibrosis, are often autosomal recessive because they require mutations in both copies of the gene

Collagen Deficiency (Haploinsufficiency)

• Father has a disease related to haploinsufficiency of a structural collagen protein
• The most likely inheritance is autosomal dominant
• Haploinsufficiency indicates having only one functional copy of the gene is insufficient, leading to dominant inheritance

Summary

• Enzyme deficiencies typically result in autosomal recessive inheritance patterns
• Structural protein disorders are more often autosomal dominant
• Focus on understanding general principles rather than memorizing specific gene-disease associations