Hyperprolinemia, Type Ii

A number sign (#) is used with this entry because hyperprolinemia type II (HYRPRO2) is caused by homozygous or compound heterozygous mutation in the pyrroline-5-carboxylate dehydrogenase gene (P5CDH; 606811) on chromosome 1p36.

For a discussion of genetic heterogeneity of hyperprolinemia, see HYRPRO1 (239500).

Clinical Features

Emery et al. (1968) described an affected mentally retarded 18-year-old girl whose retarded sister had died, presumably of the same disorder. Selkoe (1969) described a second type of hyperprolinemia with only mild mental retardation and without renal disease. Pavone et al. (1975) described 3 clinically normal sibs with type II hyperprolinemia. They lived in eastern Sicily and had first-cousin parents. All 3 also showed hyperglycinemia. The association is unexplained. No relation between proline and glycine metabolism is evident. Valle et al. (1979) found that both proline oxidase and hydroxyproline oxidase are deficient in hyperprolinemia type II.

Molecular Genetics

In 3 unrelated probands with type II hyperprolinemia, Geraghty et al. (1998) found 3 mutant alleles: 2 with frameshift mutations and 1 with a missense mutation (606811.0001-606811.0003).

Vasiliou et al. (1999) reviewed mutations in the ALDH4 gene that cause hyperprolinemia type II.