Researchers at the department of paediatric haematology in Tallaght Hospital have demonstrated the effectiveness of bone marrow transplantation in the treatment of a genetically-inherited syndrome, according to a recent paper in the medical journal Blood.
With the assistance of two Traveller families in the Republic, Dr Owen Smith and his colleagues in Tallaght Hospital joined researchers from Manchester and St Louis, US, to make the breakthrough.
The syndrome arises when a child inherits a mutated gene which normally produces an enzyme essential for the proper development of bone tissue. The mutation disturbs the proper output of the enzyme carbonic anhydrase II (CA II).
The CA II enzyme is crucial for maintaining an acid-base balance in the body and in the ongoing remodelling of bone. A deficiency of the enzyme gives rise to a syndrome which causes cerebral calcification, deficiencies in kidney function and a condition called osteopetrosis.
Osteopetrosis or marble bone disease develops as a result of a defect in bone resorption. Normally bone is in a continuous state of being laid down and reabsorbed. When this remodelling dynamic is impaired, there are a number of consequences.
First, there is narrowing of the "canals" through which cranial nerves travel within the skull; the bone marrow cavity where new blood cells are manufactured is narrowed resulting in bone marrow failure; and despite the increased density of bone it becomes "brittle" and is prone to easy fracture.
The optic nerve is affected by the narrowing in the nerve channels leading to visual impairment. Deafness is also common because of damage to the auditory nerve pathway.
CA II deficiency is an autosomal recessive inherited condition. There are 12 distinct mutations of the CA II gene, although three of these account for more than 90 per cent of all reported patients with the deficiency.
Dr Smith and his colleagues identified two Irish Traveller families who were closely related. Each has two children with reduced CA II levels and symptoms of the syndrome.
Two of the four children aged four and nine months were referred for assessment for bone marrow transplant in an attempt to prevent long-term neurological damage. Both had osteopetrosis but no cerebral calcification.
Their older siblings had unfortunately already developed irreparable neurological problems.
Gene analysis showed that both younger children had a similar mutation of the CA II gene and following matching with a sister and aunt respectively, the Dublin team carried out bone marrow transplantation.
The results, three years later, are encouraging. Theosteopetrosis in both children has resolved and cerebral calcification has been stopped in its tracks.
Bone marrow transplantation is not a universal treatment for all children with CA II deficiency. Some patients with the condition lead relatively normal lives because the gene defect is not fully expressed.
For others however, with so-called "malignant" osteopetrosis, the researchers conclude that "bone marrow transplantation should be considered and undertaken as early as possible in life to prevent long-term damage".