Urocanase Deficiency

A number sign (#) is used with this entry because of evidence that urocanase deficiency is caused by mutation in the UROC1 gene (613012) on chromosome 3q21. One such family has been reported.

Clinical Features

Yoshida et al. (1971) reported a case of urocanase deficiency. Kalafatic et al. (1980) reported 2 sisters with this deficiency. Both had severe mental retardation, short stature, blond hair, and blue eyes. They showed periods of aggression and periods of exaggerated affection-seeking. The family lived near Zagreb, Yugoslavia. The paternal grandmother and great-grandmother were regarded as 'strange' and died at 35 and 42 years, respectively. The father became obviously 'strange' at age 29 years. He was moody, 'agitated,' and aggressive toward family and neighbors. He was ataxic with dysarthric speech and died after 6 years of treatment. Autopsy showed 'encephalitis disseminata perivenosa' and diffuse cortical atrophy. Peroral loading with histidine and intravenous infusion of urocanic acid showed that the underlying metabolic defect was a block of the conversion of urocanic acid into formiminoglutamic acid (FIGLU), which is catalyzed by urocanase. Histidase was normal in liver and skin; urocanase was absent in liver. The relationship of the sisters' defect to the disorder in the ancestors in the previous 3 generations was unclear.

Espinos et al. (2009) studied a 19-year-old Spanish woman who had urocanic aciduria, mental retardation, and intermittent ataxia. She had normal development in the first year of life and walked unaided at 16 months, but the parents observed clumsy performance. At 4 years of age, she had 3 episodes of severe ataxia that lasted approximately 3 weeks each, coinciding with recurrent infections and slowly resolving over the following weeks. Brain MRIs at 5 years and 9 years of age were normal. At age 19 years, she had slight tremor and nystagmus, walked with a broad-based gait, and had very clumsy performance. Cognitive evaluation rated her IQ at 54.

Molecular Genetics

In a 19-year-old Spanish woman with urocanic aciduria, mental retardation, and ataxia, Espinos et al. (2009) identified compound heterozygosity for missense mutations in the UROC1 gene (613012.0001 and 613012.0002). The unaffected father was heterozygous for 1 of the mutations; no DNA was available from the mother. The mutations were not found in 200 ethnically matched control chromosomes.