Prolidase Deficiency

Rare autosomal recessive disorder of metabolism due to mutations in the prolidase gene. It is characterized by recurrent lower extremity skin ulcers, recurrent infections, and FACIES, often with INTELLECTUAL DISABILITY.

Also Known As:

Hyperimidodipeptiduria; Imidodipeptidase Deficiency; Deficiencies, Imidodipeptidase; Deficiencies, Prolidase; Deficiency, Imidodipeptidase; Deficiency, Prolidase; Hyperimidodipeptidurias; Imidodipeptidase Deficiencies; Prolidase Deficiencies

Networked: 122 relevant articles (2 outcomes, 9 trials/studies)

Relationship Network

Disease Context: Research Results

Congenital, Hereditary, and Neonatal Diseases and Abnormalities: 933
- Congenital Abnormalities: 25723
  - Multiple Abnormalities: 211
    - Prolidase Deficiency: 122
  - Skin Abnormalities: 159
    - Prolidase Deficiency: 122
- Inborn Genetic Diseases: 11939
  - Inborn Errors Metabolism: 1162
    - Inborn Errors Amino Acid Metabolism: 1
      - Prolidase Deficiency: 122
  - Genetic Skin Diseases: 47
    - Prolidase Deficiency: 122

Related Diseases

1.	Systemic Lupus Erythematosus (Libman-Sacks Disease)
2.	Ulcer
3.	Leg Ulcer
4.	Intellectual Disability (Idiocy)
5.	Skin Ulcer

Experts

1.	Forlino, Antonella: 11 articles (01/2020 - 10/2002)
2.	Besio, Roberta: 7 articles (01/2020 - 05/2010)
3.	Rossi, Antonio: 7 articles (03/2015 - 09/2003)
4.	Kodama, Hiroyuki: 6 articles (09/2009 - 10/2003)
5.	Weiss, Manfred S: 5 articles (04/2021 - 01/2017)
6.	Wilk, Piotr: 5 articles (04/2021 - 01/2017)
7.	Lupi, Anna: 5 articles (05/2010 - 10/2002)
8.	Liu, Gang: 5 articles (09/2009 - 01/2004)
9.	Cetta, G: 5 articles (11/2008 - 05/2000)
10.	Lupi, A: 5 articles (11/2008 - 12/2001)

Drugs and Biologics

Drugs and Important Biological Agents (IBA) related to Prolidase Deficiency:

1.	proline dipeptidase (prolidase)IBA 01/01/2020 - "This study deeply elucidates a link between prolidase activity and neuronal maturation shedding new light on the molecular basis of functional aspects in the prolidase deficiency." 01/01/1994 - "Prolidase deficiency: biochemical study of erythrocyte and skin fibroblast prolidase activity in Italian patients." 01/01/1988 - "Biochemical studies on prolidase in sera from control, patients with prolidase deficiency and their mother." 03/01/1982 - "Biochemical studies on human prolidase (EC 3.4.13.9) and prolidase deficiency are described. " 04/01/2021 - "The importance of prolidase in human health is underlined by a rare hereditary syndrome referred to as Prolidase Deficiency. "
2.	EnzymesIBA 12/13/2001 - "Deficient enzyme activity causes prolidase deficiency (PD), a rare autosomal recessive inherited disorder whose main manifestations are chronic, intractable ulcerations of the skin, particularly of lower limbs. " 07/01/1992 - "Among the genetic enzyme defects, imidopeptiduria (prolidase deficiency) caused severe clinical problems. " 04/01/1991 - "Identification of mutations in the PEPD gene from subjects with prolidase deficiency provides further insight into the physiological role and structure-function relationship of this biologically important enzyme." 01/01/1984 - "The findings indicate, for at least the present two cases, that prolidase deficiency results from an altered rather than a marked reduction in the amount of normal enzyme." 03/01/1982 - "The relative substrate specificity of the enzyme offers a reasonable explantation for the presence of a higher level of urinary imidodipeptides in a patient with prolidase deficiency. "
3.	AutoantigensIBA 12/01/2013 - "Prolidase deficiency may be associated with the loss of immune tolerance to lupus-associated autoantigens even without clinical SLE." 10/01/2007 - "In particular we discuss the role of highly increased rates of apoptosis and/or abnormal processing of apoptotic keratinocytes in prolidase deficiency and the role of C1q deficiency, which is associated with the failure of normal clearance of apoptotic cells bearing on their surfaces many of the autoantigens involved in systemic lupus erythematosus."
4.	Amino Acids FDA Link 01/01/2017 - "We hope that the recognition of this characteristic pattern of falsely elevated urinary amino acids will aid in the recognition of prolidase deficiency." 01/01/2017 - "Spurious Elevation of Multiple Urine Amino Acids by Ion-Exchange Chromatography in Patients with Prolidase Deficiency." 08/01/1977 - "Prolidase deficiency: report of a second case with quantitation of the excessively excreted amino acids." 08/01/2007 - "The first group concerns urea cycle disorders (citrullinaemia, hyperargininaemia, argininosuccinic aciduria), ketotic hyperglycinaemia, and organic acidurias (methylmalonic aciduria, glutaric aciduria type I, etc.); the second group relates to disorders of amino acid metabolism (cystathioninuria, prolidase deficiency, etc.) and transport (Fanconi syndrome, cystinurias, Hartnup syndrome, etc.). " 07/01/2005 - "The purpose of this study was to investigate the effect of various amino acids and their metabolites on the activities of prolidase I and II from human erythrocytes compared to those in a patient with prolidase deficiency. "
5.	Proline (L-Proline)FDA Link 05/01/2022 - "Obstinate leg ulceration secondary to prolidase deficiency, treated with 5% topical proline." 10/01/1992 - "Control fibroblasts were able to use iminodipeptides in lieu of proline to sustain normal growth, whereas cells homozygous for the prolidase deficiency mutation were not. " 04/19/1991 - "The synthetic iminodipeptides containing an N-terminal proline added to urine samples from a patient with prolidase deficiency were also distinguished from iminodipeptides containing a C-terminal proline in urine samples from a patient with prolidase deficiency by scanning the [M + H]+ ion of each iminodipeptide. " 12/01/1988 - "These values predict that donor erythrocytes, activated with Mn++ before transfusion could play a significant role in the recovery of proline from dietary sources of iminodipeptides in patients with prolidase deficiency." 01/01/1984 - "Two cases of prolidase deficiency showed a marked loss of activity against glycyl-proline irrespective of Mn2+ conditions. "
6.	CollagenIBA 05/01/1981 - "Studies on prolidase deficiency with a possible defect in collagen metabolism." 01/01/2023 - "Prolidase deficiency is an autosomal recessive disease that causes impaired collagen degradation. " 01/01/2022 - "Prolidase deficiency is an extremely rare, autosomal recessive disorder resulting in defective collagen formation. " 03/10/2013 - "Prolidase deficiency (PD) is a rare inborn disorder of collagen metabolism characterized by chronic recurrent cutaneous ulceration. " 01/01/1993 - "Normal production, nature, and extent of intracellular degradation of newly synthesized collagen in fibroblasts from a patient with prolidase deficiency."
7.	Proteins (Proteins, Gene)FDA Link 03/15/1998 - "The aim of this study was to examine the effects of serum iminodipeptides and prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in neutrophils from a patient with prolidase deficiency, and also to find the causative effects of superoxide on inflammatory skin lesions. " 03/15/1998 - "The effects of serum iminodipeptides and prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in neutrophils from a patient with prolidase deficiency." 08/25/1989 - "Separation of two erythrocyte prolidase isoforms by fast protein liquid chromatography; application to prolidase deficiency." 02/01/1994 - "6. A specific polyclonal antibody was raised in rabbits against the purified enzyme and immunoreactivity was investigated between rabbit antiserum and both prolidase I from various tissues and human kidney prolidase II. 7. Prolidase I from liver, erythrocytes and plasma was immunochemically identical to renal prolidase I. The polyclonal antibody did not react with prolidase II. 8. These results indicate that a specific immunoassay might be developed to investigate prolidase I protein in plasma and tissues from patients with prolidase deficiency and hepatic fibrosis." 02/23/2022 - "Prolidase deficiency (PD) is an autosomal recessive inborn multisystemic disease caused by mutations in the PEPD gene encoding the enzyme prolidase D, leading to defects in turnover of proline-containing proteins, such as collagen. "
8.	Glycine (Aminoacetic Acid)FDA LinkGeneric 06/01/1986 - "Effect of topical application of glycine and proline on recalcitrant leg ulcers of prolidase deficiency." 09/01/2006 - "[Effective therapy with a glycine-proline ointment in a patient with recurrent ulcers from prolidase deficiency]." 12/01/2004 - "The prolidase activity against methionylproline in erythrocytes from the patient with prolidase deficiency was also enhanced by glycine, L-alanine and L-serine. " 01/01/1996 - "Two ulcers in a 17-year-old girl with established prolidase deficiency were treated for 12 weeks with ointments containing amino acids in an open study comparing the effects of 5% proline and a combination of 5% proline plus 5% glycine. "
9.	Superoxides (Superoxide)IBA 11/01/1999 - "Corticosteroid treatment of prolidase deficiency skin lesions by inhibiting iminodipeptide-primed neutrophil superoxide generation." 03/15/1998 - "The aim of this study was to examine the effects of serum iminodipeptides and prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in neutrophils from a patient with prolidase deficiency, and also to find the causative effects of superoxide on inflammatory skin lesions. " 03/15/1998 - "When the neutrophils from a patient with prolidase deficiency (PDPPMN) were preincubated with prolyl-proline (Pro-Pro), which is one of the iminodipeptides found at high concentration in the serum of patients with prolidase deficiency, the N-formyl-methionyl-leucyl-phenylalanine (fMLP)-induced superoxide generation was enhanced in a concentration-dependent manner, although the extent of enhancing effect was lower than that in neutrophils from healthy humans (HPPMN). " 03/15/1998 - "The effects of serum iminodipeptides and prednisolone on superoxide generation and tyrosyl phosphorylation of proteins in neutrophils from a patient with prolidase deficiency."
10.	Ointments (Pastes)IBA 09/01/2006 - "[Effective therapy with a glycine-proline ointment in a patient with recurrent ulcers from prolidase deficiency]." 01/01/1996 - "Two ulcers in a 17-year-old girl with established prolidase deficiency were treated for 12 weeks with ointments containing amino acids in an open study comparing the effects of 5% proline and a combination of 5% proline plus 5% glycine. "

Therapies and Procedures

1.	Therapeutics 11/01/2000 - "So far, there is no efficient therapy for hereditary prolidase deficiency. " 01/01/1981 - "Prolidase deficiency with iminodipeptiduria: biochemical investigations and first results of attempted therapy." 02/01/1992 - "Blood transfusions in the therapy of a case of prolidase deficiency." 05/01/2000 - "Transient beneficial effect of GH replacement therapy and topical GH application on skin ulcers in a boy with prolidase deficiency." 04/01/1988 - "[Hereditary prolidase deficiency in 2 sisters with therapy-resistant leg ulcers]."
2.	Enzyme Replacement Therapy 12/01/1988 - "In situ activation of human erythrocyte prolidase: potential for enzyme replacement therapy in prolidase deficiency." 11/01/2008 - "Recombinant human prolidase was produced in prokaryotic and eukaryotic hosts with biochemical properties similar to the endogenous enzyme and represents a valid tool both to better understand the structure and biological function of the enzyme and to develop an enzyme replacement therapy for the prolidase deficiency (PD). "
3.	Hyperbaric Oxygenation 01/06/2017 - "Hyperbaric oxygen therapy in the management of severe leg ulcers from prolidase deficiency." 10/01/2023 - "This case presents a male patient with prolidase deficiency for 35 years whose leg ulcers were resistant to standard treatments such as wound dressings, topical treatments, and hyperbaric oxygen therapy. "
4.	Hematopoietic Stem Cell Transplantation 01/01/2012 - "Partial Rescue of Biochemical Parameters After Hematopoietic Stem Cell Transplantation in a Patient with Prolidase Deficiency Due to Two Novel PEPD Mutations."
5.	Microspheres (Microsphere) 05/01/2004 - "We have investigated whether biodegradable microspheres loaded with prolidase could release active enzyme inside cells, to consider this system as a possible therapeutic approach for prolidase deficiency. "