Ghosal hematodiaphyseal dysplasia syndrome

Alternate names

GHDD; Ghosal hematodiaphyseal dysplasia; Ghosal syndrome

Definition

Ghosal hematodiaphyseal dysplasia is a rare inherited condition characterized by abnormally thick bones and a shortage of red blood cells (anemia).

Epidemiology

Ghosal hematodiaphyseal dysplasia is a rare disorder; only a few cases have been reported in the medical literature. Most affected individuals have been from the Middle East and India.

Cause

• Ghosal hematodiaphyseal dysplasia results from mutations in the TBXAS1 gene.
• This gene provides instructions for making an enzyme called thromboxane A synthase 1, which acts as part of a chemical signaling pathway involved in normal blood clotting (hemostasis).
• Based on its role in Ghosal hematodiaphyseal dysplasia, researchers suspect that thromboxane A synthase 1 may also be important for bone remodeling, which is a normal process in which old bone is removed and new bone is created to replace it, and for the production of red blood cells in bone marrow.

Gene mutations

• Mutations in the TBXAS1 gene severely reduce the activity of thromboxane A synthase 1.
• Studies suggest that a lack of this enzyme's activity may lead to abnormal bone remodeling and fibrosis of the bone marrow.
• However, the mechanism by which a shortage of thromboxane A synthase 1 activity leads to the particular abnormalities characteristic of Ghosal hematodiaphyseal dysplasia is unclear.

Inheritance

Autosomal recessive inheritance, a 25% chance

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

Onset

Signs and symptoms of the condition become apparent in early childhood.

Signs and symptoms

• In affected individuals, the long bones in the arms and legs are unusually dense and wide.
• The bone changes specifically affect the shafts of the long bones, called diaphyses, and areas near the ends of the bones called metaphyses.
• The bone abnormalities can lead to bowing of the legs and difficulty walking.
• Ghosal hematodiaphyseal dysplasia also causes scarring (fibrosis) of the bone marrow, which is the spongy tissue inside long bones where blood cells are formed.
• The abnormal bone marrow cannot produce enough red blood cells, which leads to anemia.
• Signs and symptoms of anemia that have been reported in people with Ghosal hematodiaphyseal dysplasia include extremely pale skin (pallor) and excessive tiredness (fatigue).

Clinical presentation

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Abnormal cortical bone morphology
• Abnormal form of the vertebral bodies
• Abnormality of femur morphology(Abnormality of the thighbone)
• Abnormality of immune system physiology
• Abnormality of pelvic girdle bone morphology(Abnormal shape of pelvic girdle bone)
• Abnormality of the metaphysis(Abnormality of the wide portion of a long bone)
• Abnormality of tibia morphology(Abnormality of the shankbone)
• Anemia(Low number of red blood cells or hemoglobin)
• Bowing of the long bones(Bowed long bones)
• Craniofacial hyperostosis(Excessive bone growth of the skull and face)
• Diaphyseal thickening(Thickening of shaft or central part of long bones)

5%-29% of people have these symptoms

• Hyperostosis cranialis interna(Excessive growth of inner surface of the skull bones)
• Leukopenia(Decreased blood leukocyte number)
• Neurological speech impairment(Speech disorder)
• Splenomegaly(Increased spleen size)

Diagnosis

The diagnosis was established by clinical presentation and X-ray bone survey.

Treatment

Treatment with corticosteroids, leading to considerable improvement in anemia and bony changes, negating the need for blood transfusions. .

NIH genetic and rare disease info

• NIH info on Ghosal hematodiaphyseal dysplasia syndrome

Ghosal hematodiaphyseal dysplasia syndrome is a rare disease.

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