Marble brain disease

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.

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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.

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Clinical features

Classic triad:

• Neurological disorders (related to cerebral calcifications)
• Osteopetrosis
• Renal tubular acidosis (often combined proximal and distal, type III RTA

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Diagnosis

Imaging:

Diagnosis is based on radiological findings in the presence of acidosis and intracerebral calcifications, and can be confirmed by molecular genetic testing.