U01.01.050 X-linked recessive disorders

X-linked recessive disorders are genetic conditions caused by gene mutations on the X chromosome. These disorders primarily affect males because they have only one X chromosome. Females are typically carriers and are variably affected due to the process of X-inactivation.

Examples of X-linked Recessive Disorders

Here’s a list of common X-linked recessive disorders:

Disorder	Description
Ornithine transcarbamylase deficiency	Urea cycle disorder causing hyperammonemia.
Fabry disease	Lysosomal storage disorder causing pain, renal failure, and cardiovascular issues.
Wiskott-Aldrich syndrome	Immune deficiency characterized by eczema, thrombocytopenia, and recurrent infections.
Ocular albinism	Reduced pigmentation in the eyes leading to vision problems.
G6PD deficiency	Enzyme deficiency causing hemolytic anemia in response to oxidative stress.
Hunter syndrome	Lysosomal storage disorder affecting connective tissues, often in males.
Bruton agammaglobulinemia	Absence of mature B cells, leading to recurrent bacterial infections.
Hemophilia A and B	Deficiency in clotting factors VIII (A) or IX (B), causing bleeding disorders.
Lesch-Nyhan syndrome	Neurological and behavioral abnormalities, along with gouty arthritis.
Duchenne (and Becker) muscular dystrophy	Progressive muscle wasting, with Duchenne being more severe than Becker.

Key Concept: X-inactivation (Lyonization)

Definition: One of the two X chromosomes in females becomes transcriptionally inactive, forming a Barr body.
Importance: This process ensures dosage compensation between males and females for X-linked genes.
Impact on Carriers: Female carriers may show variable symptoms depending on whether the mutant or normal X chromosome is inactivated.

Mnemonic for X-linked Recessive Disorders

“Oblivious Female Will Often Give Her Boys Her X-Linked Disorders”

O: Ornithine transcarbamylase deficiency
F: Fabry disease
W: Wiskott-Aldrich syndrome
O: Ocular albinism
G: G6PD deficiency
H: Hunter syndrome
B: Bruton agammaglobulinemia
H: Hemophilia A and B
L: Lesch-Nyhan syndrome
D: Duchenne (and Becker) muscular dystrophy

Special Cases: X-linked Disorders in Females

Females with Turner syndrome (45, XO) are at increased risk for X-linked recessive disorders due to having only one X chromosome.

Points to Remember

X-linked recessive disorders are primarily seen in males, while females are typically carriers.
X-inactivation can result in variable expression of symptoms in female carriers.
Turner syndrome increases susceptibility to these disorders in females.
Mnemonics like “Oblivious Female Will Often Give Her Boys Her X-Linked Disorders” help in memorizing common X-linked conditions.

References

Pathoma – Genetics and Inheritance Patterns
First Aid for the USMLE Step 1 (Latest Edition)
Guyton and Hall Textbook of Medical Physiology

USMLE Step 1 Review Series

Curriculum