Partial Rescue of Biochemical Parameters After Hematopoietic Stem Cell Transplantation in a Patient with Prolidase Deficiency Due to Two Novel PEPD Mutations.

Prolidase deficiency (PD) is a rare recessive disorder resulting from mutations in the prolidase gene (PEPD); only 17 causative mutant alleles had been so far characterized. Prolidase is a ubiquitous enzyme that hydrolyses dipeptides with C-terminal proline or hydroxyproline residues and indeed, lack of this enzyme activity causes massive urine excretion of undigested iminodipeptides. The clinical manifestations of PD are widely variable, and include intractable skin ulcers, unusual face, different degree of mental retardation, and recurrent infections. No definitive treatment is at present available.We report an 8-year girl with a typical PD facies, normal intelligence, and recurrent deep ulcerations complicated by infections. She was found to be compound heterozygous for two novel mutations in PEPD, c.1133delACG and c.1301delT, affecting the C-terminal end of the enzyme where the active site is located. Given her life-threatening course, she underwent allogeneic hematopoietic stem cell transplantation (HSCT) from her HLA-identical brother, confirmed heterozygous for the c.1133delACG allele. Successful engraftment was documented by full-donor chimerism. Posttransplant monitoring of erythrocyte prolidase activity showed that the child had converted to a heterozygous pattern. Reduction of excreted urine dipeptides, evaluated by capillary electrophoresis, supported the effectiveness of the treatment. Unfortunately the patient died on day +92 of invasive fungal infection.Despite the unfavorable outcome, we provide the first evidence that HSCT has the potential to reverse some of the biochemical features of PD patients. The indication to transplant must be balanced against the clinical manifestation of individual patients.