Carnosinase deficiency: A new variant with high residual activity

Plasma carnosinase deficiency was discovered in a 12-yr-old male with profound mental retardation, severe athetoid spastic quadriparesis, optic atrophy, sensory peripheral neuropathy, and suprabulbar signs. Amino acid analysis revealed persistent carao- sinuria but no detectable carnosinemia. After ingestion of L-car- nosine (100 mg/kg), the patient had camosine in his plasma and excreted 28% of the administered load as camosine (an age- matched control excreted 13% as camosine). Urinary 1-methyl- histidine was measurable in the patient and increased greatly during a high anserine diet. Plasma carnosinase activity in the patient was 0.28 /imoles per ml plasma per hr (control mean, 2.00; range, 1.10-2.85), his parents had activity of 1.36 and 130, and 2 sibs had activities of 1.10 and 1.86. Carnosinase activity in liver from the patient was 43% of control liver. We have demonstrated that carnosinase activity is present in human nerve and that sural nerve from the patient had activity that was 46% of control nerve. Histopathologic examination of the patient’s nerve showed axonal degeneration. Histidine levels in the patient’s liver and nerve were normal, and neither β-alanine nor camosine was detectable. The unusually high residual carnosinase activity in plasma and tissues from this patient may explain his apparent ability to metabolize anserine and would suggest that this represents a new variant form of camosinase deficiency. Speculation: Carnosinuria due to plasma camosinase deficiency may be merely associated with the striking neurologic findings that have been reported rather than causally related.