#239510 ICD+
  • SNOMEDCT: 124177001
SNOMEDCT: 124177001
HYPERPROLINEMIA, TYPE II; HPII

Alternative titles; symbols
1-PYRROLINE-5-CARBOXYLATE DEHYDROGENASE DEFICIENCY

Phenotype Gene Relationships
Location Phenotype Phenotype
MIM number
Gene/Locus Gene/Locus
MIM number
1p36.13 Hyperprolinemia, type II 239510 ALDH4A1 606811


TEXT
A number sign (#) is used with this entry because the disorder is caused by mutation in the pyrroline-5-carboxylate dehydrogenase gene (P5CDH; 606811).

See also hyperprolinemia type I (239500), caused by mutation in the PRODH gene.

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.

See Also:
Flynn et al. (1989); Goodman et al. (1974); Valle et al. (1976); Valle and Phang (1974)

REFERENCES
1. Emery, F. A., Goldie, L., Stern, J. Hyperprolinaemia type 2. J. Ment. Defic. Res. 12: 187-195, 1968. [PubMed: 4972625, related citations] [Full Text: Pubget]

2. 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, related citations] [Full Text: Pubget]

3. 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, related citations] [Full Text: HighWire Press, Pubget]

4. 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, related citations] [Full Text: Pubget]

5. 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, related citations] [Full Text: Pubget]

6. Selkoe, D. J. Familial hyperprolinemia and mental retardation: a second metabolic type. Neurology 19: 494-502, 1969. [PubMed: 5815222, related citations] [Full Text: Pubget]

7. 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, related citations] [Full Text: Journal of Clinical Investigation, Pubget]

8. 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, related citations] [Full Text: Journal of Clinical Investigation, Pubget]

9. 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, related citations] [Full Text: HighWire Press, Pubget]

10. 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, related citations] [Full Text: Pubget]

Contributors: Cassandra L. Kniffin - reorganized : 4/8/2002
Victor A. McKusick - updated : 11/4/1999
Victor A. McKusick - updated : 9/17/1998
Lori M. Kelman - updated : 11/15/1996
Creation Date: Victor A. McKusick : 6/3/1986
Edit History: terry : 09/09/2010
ckniffin : 9/5/2008
carol : 4/8/2002
ckniffin : 4/8/2002
ckniffin : 4/4/2002
carol : 4/3/2001
carol : 4/3/2001
carol : 11/11/1999
carol : 11/9/1999
carol : 11/9/1999
terry : 11/4/1999
alopez : 1/25/1999
alopez : 1/13/1999
carol : 10/19/1998
carol : 9/21/1998
terry : 9/17/1998
carol : 6/23/1998
jamie : 11/15/1996
jamie : 11/6/1996
jamie : 10/25/1996
carol : 8/20/1996
mimadm : 2/19/1994
carol : 7/13/1993
supermim : 3/16/1992
supermim : 3/20/1990
ddp : 10/26/1989
root : 8/1/1989