Asunto(s)
Aberraciones Cromosómicas , Análisis Mutacional de ADN , Dipeptidasas/genética , Dermatosis de la Pierna/genética , Deficiencia de Prolidasa/genética , Úlcera Cutánea/genética , Adolescente , Adulto , Niño , Cromosomas Humanos Par 19/genética , Terapia Combinada , Dipéptidos/orina , Facies , Femenino , Estudios de Seguimiento , Humanos , Dermatosis de la Pierna/diagnóstico , Dermatosis de la Pierna/patología , Dermatosis de la Pierna/terapia , Cooperación del Paciente , Deficiencia de Prolidasa/diagnóstico , Deficiencia de Prolidasa/patología , Deficiencia de Prolidasa/terapia , Recurrencia , Análisis de Secuencia de ADN , Piel/patología , Úlcera Cutánea/diagnóstico , Úlcera Cutánea/patología , Úlcera Cutánea/terapia , Adulto JovenRESUMEN
Prolidase deficiency is a rare autosomal recessive disorder characterized by recurrent and nonhealing skin ulcers along with facial dysmorphism and mental retardation. We report a 13-year-old girl who has clinical manifestation of Proliodase deficiency. It is a very rare disorder and no such case has been reported so far from Pakistan.
Asunto(s)
Dipeptidasas/metabolismo , Deficiencia de Prolidasa/diagnóstico , Administración Tópica , Adolescente , Femenino , Glucocorticoides/uso terapéutico , Glicina/administración & dosificación , Humanos , Plasmaféresis , Deficiencia de Prolidasa/metabolismo , Deficiencia de Prolidasa/terapia , Prolina/administración & dosificaciónRESUMEN
BACKGROUND: Prolidase Deficiency (PD) is a rare hereditary disease consisting in developmental delay, mental retardation, facial dysmorphism, splenomegaly, recurrent pulmonary infections and skin lesions. CASE REPORT: The present study reports a case of PD treated in the Paediatric Section of the Department of Dentistry and Surgery at the University of Bari. A special diagnostic and clinical approach to the patient was useful to improve his quality of life and identify some new aspects of this systemic disease. In particular, clinical features never described before are reported: low hair line, decreased osteotendinous reflexes, long upper lip, microrhinia, dentoskeletal Class III, dental age (Proffit) older than chronological age, fusion of 2nd and 3rd cervical vertebrae, incomplete atlanto-occipital fusion.
Asunto(s)
Cara , Deficiencia de Prolidasa/complicaciones , Anomalías Dentarias/etiología , Cefalometría , Niño , Humanos , Masculino , Deficiencia de Prolidasa/terapia , Radiografía PanorámicaRESUMEN
Prolidase is the only human enzyme responsible for the digestion of iminodipeptides containing proline or hydroxyproline at their C-terminal end, being a key player in extracellular matrix remodeling. Prolidase deficiency (PD) is an intractable loss of function disease, characterized by mutations in the prolidase gene. The exact causes of activity impairment in mutant prolidase are still unknown. We generated three recombinant prolidase forms, hRecProl-231delY, hRecProl-E412K and hRecProl-G448R, reproducing three mutations identified in homozygous PD patients. The enzymes showed very low catalytic efficiency, thermal instability and changes in protein conformation. No variation of Mn(II) cofactor affinity was detected for hRecProl-E412K; a compromised ability to bind the cofactor was found in hRecProl-231delY and Mn(II) was totally absent in hRecProl-G448R. Furthermore, local structure perturbations for all three mutants were predicted by in silico analysis. Our biochemical investigation of the three causative alleles identified in perturbed folding/instability, and in consequent partial prolidase degradation, the main reasons for enzyme inactivity. Based on the above considerations we were able to rescue part of the prolidase activity in patients' fibroblasts through the induction of Heath Shock Proteins expression, hinting at new promising avenues for PD treatment.
