General description (for patients): Infants with this disorder are often jaundiced and have enlarged livers and spleens. A skin rash and even skin ulcers, especially on the legs, occur in young children. Anemia and digestive problems with diarrhea, vomiting, and dehydration are often seen. Repeated infections are common. The facies are characteristic with prominent and widely-spaced eyes, a high forehead and a flat bridge of the nose. Mental development may be delayed.
Medical description: This disorder presents with multisystem features including petechiae, anemia, thrombocytopenia, severe infections, skin rash, hepatosplenomegaly, and neonatal jaundice. The facies is characteristic with a prominent forehead, hypertelorism, a flat nasal bridge, and proptosis. Most patients have some mental delay but this is variable. Chronic leg ulcers are often reported. Increased susceptibility to infections is a feature probably secondary to as yet undetermined immunologic deficiencies. There is considerable biochemical heterogeneity in this disorder with little clinical correlation. Peptidase D is an important enzyme in the degradation of both endogenous and dietary proteins with C-terminal proline and hydroxyproline. Massive imidodipeptiduria is diagnostic.
GENETICS: This is an autosomal recessive disorder caused by mutations in the PEPD gene on chromosome 19 (19q12-q13.11) encoding the enzyme peptidase D. A homozygous nonsense mutation (793T>C) resulting in a premature stop codon has been identified among Amish children in Geauga County, Ohio.
TREATMENT: No treatment has been found.
PROGNOSIS: Insufficient numbers of patients have been reported to determine the prognosis. Some developmental delay seems to be a feature at least in children. Few adults with this disorder have been reported.
ANCILLARY TREATMENTS AND SUPPORT: Prompt treatment of infections, dehydration, diarrhea and anemia is important.
SPECIALISTS AND SPECIALTY CENTERS: Pediatrician, gastroenterologist, nutritionist, neurologist.
Wang, H., Kurien, B.T., Lundgren, D., Patel, N.C., Kaufman, K.M., Miller, D.L., Porter, A.C., D’Souza, A., Nye, L., Tumbush, J., Hupertz, V., Kerr, D.S., Kurono, S., Matsumoto, H., and Scofield, R.H.: A nonsense mutation of PEPD in four Amish children with prolidase deficiency. Am. J. Med. Genet. 140A: 580-585, 2006. PubMed ID: 16470701
Kurien, B.T., Patel, N.C., Porter, A.C., D'Souza, A, Miller, D., Matsumoto, H., Wang, H. and Scofield, R.H.: Prolidase deficiency and biochemistry assays used in its diagnosis. Analytic Biochemistry. 349: 165-176, 2006. PubMed ID: 16298626
Ledoux, P., Scriver, C.R., and Hechtman, P.: Expression and molecular analysis of mutations in prolidase deficiency. Am. J. Hum. Genet. 59: 1035-1039, 1996. PubMed ID: 8900231