Aase syndrome

Overview

Aase syndrome is a rare congenital disorder characterized by a combination of anemia (a reduced number of red blood cells) and distinct physical abnormalities. The anemia seen in Aase syndrome is usually present at birth or in early infancy and is classified as a type of hypoplastic anemia, meaning the bone marrow produces fewer blood cells than normal. This condition may also be associated with malformations of the limbs, head, and facial features. It is sometimes considered a variant of Diamond–Blackfan anemia due to overlapping characteristics.

Causes

The exact cause of Aase syndrome is not fully understood, but in many cases, it appears to follow an autosomal dominant inheritance pattern. Some instances may arise spontaneously (de novo) with no prior family history. The genetic defect likely involves abnormalities in ribosomal proteins or genes related to bone marrow function, although a specific gene mutation has not been conclusively identified in all cases. In certain families, mutations in the RPS19 gene—also implicated in Diamond–Blackfan anemia—have been associated with Aase syndrome.

Symptoms

Signs and symptoms of Aase syndrome can vary but typically include a combination of blood-related and physical features:

Hematologic Features:

• Congenital hypoplastic anemia (usually evident in infancy)

• Fatigue or pallor due to low red blood cell count

• Delayed growth and development in some cases

Physical Features:

• Triphalangeal thumbs (thumbs with three bones, resembling fingers)

• Absent or underdeveloped thumbs

• Narrow shoulders or limited shoulder movement

• Low-set ears or other minor facial anomalies

• Cleft palate (in rare cases)

• Skin folds at the inner corners of the eyes (epicanthal folds)

• Increased joint mobility (hypermobility)

Diagnosis

Diagnosis of Aase syndrome is based on a combination of clinical evaluation, blood tests, and family history. Diagnostic steps include:

• Complete blood count (CBC): Shows anemia with reduced red blood cell production

• Bone marrow biopsy: Reveals reduced red blood cell precursors (hypoplastic marrow)

• Physical examination: Identifies characteristic skeletal and facial anomalies

• Genetic testing: May identify mutations associated with ribosomal function or inherited anemia syndromes

• Family history assessment: To determine possible inheritance patterns

Treatment

Treatment of Aase syndrome is tailored to the individual’s needs, particularly to manage anemia and support growth and development. Standard treatment strategies include:

• Red blood cell transfusions: Used in early infancy to treat severe anemia

• Corticosteroids: May help stimulate red blood cell production in some patients

• Bone marrow transplant: Considered in severe, transfusion-dependent cases with compatible donors

• Supportive care: Nutritional support, physical therapy, and surgical correction for physical anomalies if necessary

• Monitoring for complications: Including iron overload from repeated transfusions (may require chelation therapy)

Prognosis

The prognosis for individuals with Aase syndrome varies depending on the severity of anemia and presence of congenital abnormalities. Many children respond well to early treatment, especially with red blood cell transfusions and steroid therapy. In some cases, anemia may improve with age. Those with more severe forms may require long-term medical care, including bone marrow transplantation. Life expectancy can be normal with effective management, although regular follow-up is essential to monitor blood health and growth.