Syndrome consisting primarily of renal tubular acidosis, cerebral calcification and osteopetrosis.
- Autosomal recessive inheritance (8q22)
- M/C in the Arab Gulf region, with what is known as an ‘Arabic mutation‘
History:
The association of osteopetrosis with renal tubular acidosis (RTA) was first described in 1972, and it is also referred to as Guibaud-Vainsel syndrome or marble brain disease or carbonic anhydrase II deficiency syndrome.
Pathophysiology
Carbonic anhydrase-II (CA-II):
Zinc metallo-enzyme that catalyzes the reversible hydration of CO2 to form carbonic acid (H2CO3)
CA-II has a wide tissue distribution, being found in bone, kidney (proximal tubules and collecting duct), erythrocytes and glial cells, with osteoclasts being particularly rich in CA-II.
Deficiency of CA-II impairs the production of H + by the osteoclasts and, thus, bone resorption is blocked, leading to the development of osteopetrosis.
Clinical features
Classic triad:
- Neurological disorders (related to cerebral calcifications)
- Osteopetrosis
- Renal tubular acidosis (often combined proximal and distal, type III RTA
Diagnosis
Imaging:
Diagnosis is based on radiological findings in the presence of acidosis and intracerebral calcifications, and can be confirmed by molecular genetic testing.


