Autosomal Recessive Disorders Lecture Notes

Key Characteristics of Autosomal Recessive Disorders

• Childhood Onset: These disorders typically manifest from childhood.
• Complete Penetrance: 100% penetrance meaning everyone with the genotype will manifest the disease.
  • Unlike autosomal dominant disorders where penetrance is incomplete.
• Narrow Expressivity: All patients show similar symptoms, unlike the wide expressive variability seen in autosomal dominant conditions.

Examples of Autosomal Recessive Disorders

• Disorders often end with "-uria" or "-emia":
  • Phenylketonuria (PKU)
  • Alkaptonuria
  • Homocystinuria
  • Sickle Cell Anemia

Other Autosomal Recessive Disorders

• Albinism
• Congenital Adrenal Hyperplasia: Can lead to female pseudohermaphroditism.
• Friedreich's Ataxia
• Wilson's Disease: Copper overload.
• Hemochromatosis: Iron overload.
• Cystic Fibrosis: CFTR gene mutation, defective chloride channels.
• Ataxia Telangiectasia
• Fanconi Anemia
• Xeroderma Pigmentosum
• Bloom Syndrome
• Alpha-1 Antitrypsin Deficiency: Can lead to emphysema.

Metabolic Disorders with Autosomal Recessive Inheritance

• Lysosomal Storage Diseases (LSDs)
• Glycogen Storage Diseases

Exceptions

• Fabry's Disease and Hunter's Syndrome: Follow X-linked recessive inheritance.

Specific Disorders and Related Points

Phenylketonuria (PKU)

• Caused by deficiency of phenylalanine hydroxylase.

Alkaptonuria

• Caused by deficiency of homogentisic acid oxidase leading to cartilage discoloration (ochronosis).

Lysosomal Storage Disorders

Tay-Sachs Disease

• Hexosaminidase A deficiency resulting in GM2 ganglioside accumulation.
• Symptoms include developmental delay, cherry-red spot in retina, onion skin lysosomes.

Niemann-Pick Disease

• Sphingomyelinase deficiency; sphingomyelin accumulation.
• Presents with cherry-red spot, hepatosplenomegaly, and zebra bodies in lysosomes.

Gaucher's Disease

• Beta-glucocerebrosidase deficiency.
• Symptoms include bone pain, hepatosplenomegaly, and crumpled tissue paper appearance of cells.

Inheritance Patterns and Risks

• Autosomal recessive disorders require inheritance of two recessive alleles (one from each parent).
• Consanguinity increases risk; common in families with consanguineous marriages.
• Skipping of Generations: Not every generation is affected, unlike autosomal dominant patterns.