Prolidase deficiency: biochemical study of erythrocyte and skin fibroblast prolidase activity in Italian patients

BACKGROUND AND METHODS: Prolidase deficiency (PD), a rare, autosomally inherited disorder causing iminodipeptiduria is associated with a number of clinical manifestations, the principle feature being chronic skin ulceration. The enzyme prolidase cleaves iminodipeptides containing C-terminal prolyl or hydroxyprolyl residues and is important in the final stages of protein catabolism. We report clinical and biochemical findings in 8 Italian patients with proven prolidase deficiency. There was considerable heterogeneity in age at onset of symptoms (varying from 3-17 years), mental retardation and clinical manifestations (asymptomless to very severe). Prolidase activity was determined in hemolysates of patient erythrocytes and cultured dermal fibroblasts. RESULTS: Prolidase activity was found to be deficient, especially against gly-pro. Erythrocyte and fibroblast enzyme was also separated into two forms, a major isoform (I) and a minor one (II) by fast protein liquid chromatography, and activity against different iminodipeptide substrates was tested. Isoform I activity was markedly reduced in all patients as compared to normal controls, while isoform II activity appeared to be unaltered. CONCLUSIONS: We were unable to find any correlation between degree of enzyme activity loss and severity of symptoms

Recurrent infections with IgG2 deficiency.

An 11 year old girl with retarded growth, recurrent infections, bronchiectasis, and normal serum immunoglobulin concentrations had a combined deficit of the IgG2 subclass and IgG and IgM specific antibodies. Immunoglobulin replacement was followed by clinical improvement. The importance of determining both IgG subclasses and antibody activity in patients with recurrent infections and normal serum immunoglobulin values is emphasised

Recurrent infections with IgG2 deficiency.

An 11 year old girl with retarded growth, recurrent infections, bronchiectasis, and normal serum immunoglobulin concentrations had a combined deficit of the IgG2 subclass and IgG and IgM specific antibodies. Immunoglobulin replacement was followed by clinical improvement. The importance of determining both IgG subclasses and antibody activity in patients with recurrent infections and normal serum immunoglobulin values is emphasised

Clinical eterogeneity and reversibility of selective immunoglobulin A deficiency in 80 children.

80 children with selective immunoglobulin A (IgA) deficiency--40 with severe deficiency (serum IgA less than 5 mg/dl) and 40 with partial deficiency (serum IgA greater than 5 mg/dl but less than minus 2 SD of the age-normal mean)--were followed up for 1.5 to 9 years; during which their serum and salivary IgA levels were measured periodically and the number and type of infections they had were recorded. In the partial deficiency group serum IgA rose to normal levels in half the group at a median age of 14 years and at a median time of 4 years after diagnosis, but they did not reach the normal range in the severe deficiency group. Pneumonia occurred more frequently in the severe than in the partial deficiency group. In addition, 11 of the 12 severely IgA deficient patients who had pneumonia had levels of both serum and salivary IgA of less than 0.5 mg/dl, and only 1 had detectable serum IgA levels. These data indicate that in childhood severe IgA deficiency is persistent and predisposed to pneumonia, whereas partial IgA deficiency is often transient and only occasionally associated with pneumonia

[Granulocyte disorders].

The various "in vitro" tests for evaluating polymorphonuclear leucocyte function in children with recurrent infections are described and the different clinical conditions caused or accompanied by defects in polymorphonuclear function are summarized briefly. The necessity of correct interpretation of the results of the laboratory tests used in the diagnostic evaluation of patients with suspected immunodeficiency is stressed

Transient beneficial effect of GH replacement therapy and topical GH application on skin ulcers in a boy with prolidase deficiency.

A diagnostic examination for short stature in a boy with chronic ulcers of the feet due to prolidase deficiency, a rare disorder associated with intractable ulcers of the skin, led to the diagnosis of growth hormone (GH) deficiency. Replacement treatment with r-hGH associated with the topical application of a GH-containing ointment when the boy was 13 years old resulted in complete but transitory healing of the ulcers, which can probably be attributed to the growth-promoting effects of GH on dermal connective tissue