Autosomal Recessive (AR) Disorders
AR disorders require two mutant alleles (homozygous state) for phenotypic expression. They typically involve enzyme deficiencies, whereas autosomal dominant disorders often involve structural protein defects.
1. Common AR Patterns
- Inheritance: Typically affects siblings (horizontal transmission).
- Parents: Usually asymptomatic carriers (obligate heterozygotes).
- Risk: 25% risk of recurrence for each pregnancy of carrier parents.
2. High-Yield AR Disorders
| Category | Examples |
|---|---|
| Metabolic | Phenylketonuria (PKU), Galactosemia, Wilson’s disease, and Hemochromatosis. |
| Hematologic | Sickle cell anemia, Thalassemia. |
| Pulmonary/GI | Cystic Fibrosis (CF). |
| Endocrine | Congenital Adrenal Hyperplasia (CAH). |
3. Consanguinity
AR disorders are significantly more common in populations with high rates of consanguineous marriages, as this increases the likelihood of both parents sharing the same recessive mutant allele.
NEET PG Hint: Remember that most inborn errors of metabolism follow an AR pattern. When you see a clinical vignette involving a child with failure to thrive, developmental delay, or unexplained acidosis/seizures, strongly consider an underlying AR metabolic disorder. If a disease is extremely rare, it is almost always AR.