Alternative titles; symbols
SNOMEDCT: 124177001, 717181004; ORPHA: 79101; DO: 0080543;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 1p36.13 | Hyperprolinemia, type II | 239510 | Autosomal recessive | 3 | ALDH4A1 | 606811 |
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).
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.
The transmission pattern of HYRPRO2 in the families reported by Geraghty et al. (1998) was consistent with autosomal recessive inheritance.
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.
Emery, F. A., Goldie, L., Stern, J. Hyperprolinaemia type 2. J. Ment. Defic. Res. 12: 187-195, 1968. [PubMed: 4972625] [Full Text: https://doi.org/10.1111/j.1365-2788.1968.tb00258.x]
Flynn, M. P., Martin, M. C., Moore, P. T., Stafford, J. A., Fleming, G. A., Phang, J. M. Type II hyperprolinaemia in a pedigree of Irish Travellers (nomads). Arch. Dis. Child. 64: 1699-1707, 1989. [PubMed: 2624476] [Full Text: https://doi.org/10.1136/adc.64.12.1699]
Geraghty, M. T., Vaughn, D., Nicholson, A. J., Lin, W.-W., Jimenez-Sanchez, G., Obie, C., Flynn, M. P., Valle, D., Hu, C. A. Mutations in the delta-1-pyrroline 5-carboxylase dehydrogenase gene cause type II hyperprolinemia. Hum. Molec. Genet. 7: 1411-1415, 1998. [PubMed: 9700195] [Full Text: https://doi.org/10.1093/hmg/7.9.1411]
Goodman, S. I., Mace, J. W., Miles, B. S., Teng, C. C., Brown, S. B. Defective hydroxyproline metabolism in type II hyperprolinemia. Biochem. Med. 10: 329-336, 1974. [PubMed: 4851275] [Full Text: https://doi.org/10.1016/0006-2944(74)90036-2]
Pavone, L., Mollica, F., Levy, H. L. Asymptomatic type II hyperprolinaemia associated with hyperglycinaemia in three sibs. Arch. Dis. Child. 50: 637-641, 1975. [PubMed: 1200680] [Full Text: https://doi.org/10.1136/adc.50.8.637]
Selkoe, D. J. Familial hyperprolinemia and mental retardation: a second metabolic type. Neurology 19: 494-502, 1969. [PubMed: 5815222] [Full Text: https://doi.org/10.1212/wnl.19.5.494]
Valle, D., Goodman, S. I., Applegarth, D. A., Shih, V. E., Phang, J. M. Type II hyperprolinemia: delta-1-pyrroline-5-carboxylic acid dehydrogenase deficiency in cultured skin fibroblasts and circulating lymphocytes. J. Clin. Invest. 58: 598-603, 1976. [PubMed: 956388] [Full Text: https://doi.org/10.1172/JCI108506]
Valle, D., Goodman, S. I., Harris, S. C., Phang, J. M. Genetic evidence for a common enzyme catalyzing the second step in the degradation of proline and hydroxyproline. J. Clin. Invest. 64: 1365-1370, 1979. [PubMed: 500817] [Full Text: https://doi.org/10.1172/JCI109593]
Valle, D. L., Phang, J. M. Type 2 hyperprolinemia: absence of delta-1-pyrroline-5-carboxylic acid dehydrogenase activity. Science 185: 1053-1054, 1974. [PubMed: 4369405] [Full Text: https://doi.org/10.1126/science.185.4156.1053]
Vasiliou, V., Bairoch, A., Tipton, K. F., Nebert, D. W. Eukaryotic aldehyde dehydrogenase (ALDH) genes: human polymorphisms, and recommended nomenclature based on divergent evolution and chromosomal mapping. Pharmacogenetics 9: 421-434, 1999. [PubMed: 10780262]