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European Journal of Pediatrics

, Volume 169, Issue 6, pp 727–732 | Cite as

Prolidase deficiency: it looks like systemic lupus erythematosus but it is not

  • Aharon KlarEmail author
  • Paulina Navon-Elkan
  • Alan Rubinow
  • David Branski
  • Haggit Hurvitz
  • Ernst Christensen
  • Morad Khayat
  • Tzipora C. Falik-Zaccai
Original Paper

Abstract

Three siblings with recalcitrant leg ulceration, splenomegaly, photosensitive rash, and autoantibodies were suspected of having prolidase deficiency. Urine was checked for iminodipeptiduria, fibroblasts were cultured and analyzed for prolidase activity, and DNA was extracted for identifying the causative mutation. Glycyl proline was found as the dominant dipeptide in the urine. The activity of proline dipeptidase in fibroblasts was 2.5% of control fibroblasts. Sequence analysis of the PEPD gene revealed a homozygous nonsense C→G transition at nucleotide 768. In conclusion, prolidase deficiency was diagnosed in siblings with skin ulceration autoantibodies and a lupus-like disease. A novel nonsense mutation was found, associated with the severe outcome of our patients.

Keywords

Systemic lupus erythematosus (SLE) Prolidase deficiency Mutation 

Notes

Acknowledgments

We would like to thank N. Alon and L. Golan for their editorial assistance.

Conflict of Interest

The authors declare that they have no conflict of interest, financial or otherwise, in connection with the paper.

References

  1. 1.
    Beck B, Christensen E, Brandt NJ (1981) Forminoglutamic aciduria in a slightly retarded boy with chronic obstructive lung disease. J Inher Metabol Dis 4:225–228CrossRefGoogle Scholar
  2. 2.
    Ben-Bassat H, Eldad A, Chaouat M et al (1992) Structural and functional evaluation of modifications in the composite skin graft: cryopreserved dermis and cultured keratinocytes. Plast Reconstr Surg 89:510–520CrossRefPubMedGoogle Scholar
  3. 3.
    Bissonete R, Friedmann D, Giroux JM et al (1993) Prolidase deficiency: a multisystemic hereditary disorder. J Am Acad Dermatol 29:818–821CrossRefGoogle Scholar
  4. 4.
    Chen KR, Carlson JA (2008) Clinical approach to cutaneous vasculitis. Am J Clin Dermatol 9:71–92CrossRefPubMedGoogle Scholar
  5. 5.
    Christensen E (1983) Improved assay of glutaryl-CoA dehydrogenase in cultured cells and liver: application to glutaric aciduria type I. Clin Chim Acta 129:91–97CrossRefPubMedGoogle Scholar
  6. 6.
    Di Rocco M, Fanmtasia AR, Taro M et al (2007) Systemic lupus erythematosus-like disease in a 6-year-old boy with prolidase deficiency. J Inherit Metab Dis 30:814CrossRefPubMedGoogle Scholar
  7. 7.
    Falik-Zaccai TC, Khayat M, Luder A et al (Mar 23 2009) A broad spectrum of developmental delay in a large cohort of prolidase deficiency patients demonstrates marked interfamilial and intrafamilial phenotypic variability. Am J Med Genet B Neuropsychiatr Genet (in press)Google Scholar
  8. 8.
    Goodman SI, Solomons CC, Muschenheim F et al (1968) A syndrome resembling lathyrism associated with iminodipeptiduria. Am J Med 45:152–159CrossRefPubMedGoogle Scholar
  9. 9.
    Hershkovitz T, Hassoun G, Indelman M et al (2006) A homozygous missense mutation in PEPD encoding peptidase D causes prolidase deficiency associated with hyper-IgE syndrome. Clin Exp Dermatol 31:435–440CrossRefPubMedGoogle Scholar
  10. 10.
    Jackson SH, Dennis AW, Greenberg M (1975) Iminodipeptiduria. A genetic defect in recycling collagen; a method for determining prolidase in erythrocytes. Can Med Assoc J 113:759–763PubMedGoogle Scholar
  11. 11.
    Jemec GB, Moe AT (1996) Topical treatment of skin ulcres in prolidase deficiency. Pediatr Dermatol 13:58–60CrossRefPubMedGoogle Scholar
  12. 12.
    Johnstone RAW, Povall JT, Baty D (1974) Determination of dipeptides in urine. Clin Chim Acta 52:137–142CrossRefPubMedGoogle Scholar
  13. 13.
    Kurien BT, Patel NC, Porter AC et al (2006) Prolidase deficiency and the biochemical assays used in its diagnosis. Anal Biochem 349:165–175CrossRefPubMedGoogle Scholar
  14. 14.
    Lopes I, Marques L, Neves E et al (2002) Prolidase deficiency with hyperimmunoglobulin E: a case report. Pediatr Allergy Immunol 13:140–142CrossRefPubMedGoogle Scholar
  15. 15.
    Lupi A, Rossi A, Campari E et al (2006) Molecular characterization of six patients with prolidase deficiency: identification of the first small duplication in the prolidase gene and of a mutation generating symptomatic and asymptomatic outcomes within the same family. J Med Genet 43:e58CrossRefPubMedGoogle Scholar
  16. 16.
    Lupi A, Tenni R, Rossi A et al (2008) Human prolidase and prolidase deficiency: an overview on the characterization of the enzyme involved in proline recycling and on the effects of its mutations. Amino Acids 35:739–752CrossRefPubMedGoogle Scholar
  17. 17.
    Maricq HR, Spencer-Green G, Leryo EC (1987) Skin capillary abnormalities as indicators of organ involvement in scleroderma (systemic sclerosis), Raynaud’s syndrome and dermatomyositis. Am J Med 61:862–870CrossRefGoogle Scholar
  18. 18.
    Myara I, Charpentier C, Lemonnier (1987) Prolidase and prolidase deficiency. A mini review. Life Sci 34:1985–1998CrossRefGoogle Scholar
  19. 19.
    Pedersen PS, Christensen E, Brandt NJ (1983) Prolidase deficiency. Acta Paediatr Scand 72:785CrossRefPubMedGoogle Scholar
  20. 20.
    Powell GP, Rasco MA, Maniscalco RM (1974) A prolidase deficiency in man with iminopeptiduria. Metabolism 23:505–513CrossRefPubMedGoogle Scholar
  21. 21.
    Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning. A laboratory manual. Cold Spring Harbor Laboratory Press, New YorkGoogle Scholar
  22. 22.
    Sheffield LJ, Schlesinger P, Faull K et al (1997) Iminopeptiduria, skin ulceration, and edema in a boy with prolidase deficiency. J Pediatr 91:578–583Google Scholar
  23. 23.
    Shrinath M, Walter JH, Haeney M et al (1997) Prolidase deficiency and systemic lupus erythematosus. Arch Dis Child 76:441–444CrossRefPubMedGoogle Scholar
  24. 24.
    Tan EM, Cohen AS, Fries JF et al (1982) The1982 revised criteria for the classification of systemic lupus erythematosus. Arthritis Rheum 25:1271–1277CrossRefPubMedGoogle Scholar
  25. 25.
    Wang H, Kurien BT, Lundgrn D et al (2006) A nonsense mutation of PEPD in four Amish children with prolidase deficiency. Am J Med Genet A 140:580–585PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  • Aharon Klar
    • 1
    • 8
    Email author
  • Paulina Navon-Elkan
    • 1
    • 6
  • Alan Rubinow
    • 2
  • David Branski
    • 1
    • 7
  • Haggit Hurvitz
    • 1
  • Ernst Christensen
    • 3
  • Morad Khayat
    • 4
  • Tzipora C. Falik-Zaccai
    • 4
    • 5
  1. 1.Department of PediatricsBikur Cholim General HospitalJerusalemIsrael
  2. 2.Division of Rheumatology, Department of Internal MedicineHadassah Medical CenterJerusalemIsrael
  3. 3.Metabolic LaboratoryDepartment of Clinical Genetics Juliane Marie CentreCopenhagenDenmark
  4. 4.Institute of Human GeneticsWestern Galilee HospitalNahariaIsrael
  5. 5.Rappaport Faculty of Medicine, TechnionIsrael Institute of TechnologyHaifaIsrael
  6. 6.Pediatric Day CareShaare Zedek Medical CenterJerusalemIsrael
  7. 7.Department of PediatricsHadassah University HospitalJerusalemIsrael
  8. 8.Pediatrics Gastroenterology Unit, Department of PediatricsBikur Cholim General HospitalJerusalemIsrael

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