Aase syndrome

Synonyms

4

Overview

Aase syndrome is a rare inherited disorder characterized by anemia with some joint and skeletal deformities. Aase syndrome is thought to be an autosomal recessive inherited disorder. The genetic basis of the disease is not known. The anemia is caused by underdevelopment of the bone marrow, which is where blood cells are formed.

It is named after the American paediatricians Jon Morton Aase and David Weyhe Smith, who characterized it in 1968.

Symptoms

  • Mildly slowed growth
  • Pale skin
  • Delayed closure of fontanelles (soft spots)
  • Narrow shoulders
  • Triple jointed thumbs, absent or small knuckles, decreased skin creases at finger joints
  • Inability to fully extend the joints from birth (congenital contractures)
  • Cleft palate
  • Deformed ears
  • Droopy eyelids

Causes

Most cases of Aase syndrome occur without a known reason and are not passed down through families (inherited). However, some cases have been shown to be inherited.

The anemia in Aase syndrome is caused by poor development of the bone marrow, which is where blood cells are formed.

Several genes (RPL5, RPL11, RPL35A, RPS7, RPS10,RPS17, RPS19, RPS24, and RPS26) have been identified whose mutation cause Aase syndrome. These genes provide instructions for making several of the approximately 80 different ribosomal proteins, which are components of cellular structures called ribosomes. Ribosomes process the cell's genetic instructions to create proteins. 

Mutations in any of the genes listed above are believed to affect the stability or function of the ribosomal proteins. Studies indicate that a shortage of functioning ribosomal proteins may increase the self-destruction of blood-forming cells in the bone marrow, resulting in anemia. Abnormal regulation of cell division or inappropriate triggering of apoptosis may contribute to the other health problems that affect some people with aase syndrome.

Prevention

As with most genetic diseases there is no way to prevent the entire disease. With prompt recognition and treatment of infections in childhood, the complications of low white blood cell counts may be limited.

Genetic counseling is recommended if you have a family history of the syndrome and wish to become pregnant.

Diagnosis

  • A CBC (complete blood count) will show anemia and a decrease in the white blood cell count.
  • An echocardiogram may reveal heart defects (ventricular septal defect is most common).
  • X-rays will show skeletal abnormalities as described above.
  • A bone marrow biopsy may be performed.

Prognosis

Anemia usually resolves over the years.

Complications

• Complications related to anemia include weakness, fatigue, and decreased oxygenation of the blood.
• Decreased white blood cells alter the body's ability to fight infection.
• If a heart defect exists, it may cause multiple complications (depending on the specific defect).
• Severe cases have been associated with still birth or early death.

Treatment

  • Frequent blood transfusions are given in the first year of life to treat anemia.
  • Prednisone may be given, although this should be avoided in infancy because of side effects on growth and brain development.
  • A bone marrow transplant may be necessary if other treatment fails.

Resources

  • NIH