Alpha Thalassemia, X-Linked

Alpha Thalassemia/Mental Retardation, X-Linked
Alpha Thalassemia/Mental Retardation, X-Linked

Overview Of Alpha Thalassemia, X-Linked

Alpha thalassemia is an x-linked inherited disorder that affects many different parts of the body. This condition appears almost exclusively in males.

Symptoms Of Alpha Thalassemia 

Those with alpha thalassemia suffer from delayed development and an intellectual disability. They often have significant delays to their acquisition of speech, and most never manage more than a few spoken or signed words.

Hypotonia (weakened muscle tone) is also a prime symptom. This can lead to delayed motor skills such as walking, standing, and sitting. Some more severely affected people may never be able to walk independently.

Alpha thalassemia has associated distinctive facial features. Examples of these include a small nose with upturned nostrils, wider than average spaced eyes, and low set ears on the head. Also, their upper lip can be shaped somewhat like an upside-down V, and their lower lip tends to be quite prominent. These features are most noticeable in the person’s early childhood, and then tend to change with age. Adults tend to have a flatter than average face, with a short nose.

Additional Symptoms

Most people with the disorder will have mild cases of a blood disorder called agenerative anemia. This disorder causes the person’s body to reduce its production of hemoglobin. This protein normally works within red blood cells to carry oxygen throughout the body. Without enough hemoglobin, the person’s tissues may become starved of oxygen.

In some cases, those with alpha thalassemia can have a different version of anemia. This version results from a simple shortage of red blood cells, which causes weakness, fatigue, and pale skin in the person.

Additional features of x-linked alpha thalassemia can include a short stature, microcephaly (a small head size), and abnormalities of the skeletal system. Many have issues with their digestive system, such as gastroesophageal reflux (a backflow of stomach acid into the esophagus) and chronic constipation. Some may also have abnormalities of their genital area, such as hypospadias (where the penis has a urethral opening on the underside and the testes did not descend fully.) In more severe cases of abnormality, ambiguous genitalia may occur. This means it’s not fully clear if the genitals are male or female.

Commonly Associated With

ATR-X syndrome, ATRX syndrome, XLMR-hypotonic face syndrome

Cause Of Alpha Thalassemia, X-Linked

X-linked alpha thalassemia intellectual disability syndrome occurs due to mutations in the ATRX gene. This gene provides instructions that are essential to the production of a protein that’s necessary for normal development. The exact function of this ATRX-associated protein is unknown. It may help regulate the HBA1 and HBA2 genes, which are necessary for the normal production of hemoglobin.  


This particular condition is pretty rare. Worldwide, only around 200 affected individuals have been reported. Its exact prevalence is currently unknown.

The ATRX gene is located on the X chromosome, which is why it’s considered an X-linked disorder. It’s also a recessive pattern of inheritance. Males only have one X chromosome, instead of the two that females have. Because of this, males only need one abnormal copy of the ATRX gene to have the condition. This makes them far more likely to have the condition than females, who may have one abnormal copy of the ATRX gene on their X chromosome, but may have another normal copy on their other X chromosome. One working copy is enough to avoid the syndrome entirely.

X-linked inheritance means that fathers cannot possibly pass any X-linked traits to their sons. This applies to most X-linked disorders, not just this one.