Pulmonary manifestations of prolidase deficiency.

BACKGROUND: Prolidase deficiency is a rare autosomal recessive disease, in which pulmonary manifestations have been sporadically reported. AIMS: We have encountered two patients who presented with severe pulmonary cystic lesions leading to respiratory failure. This led us to retrospectively evaluate pulmonary involvement in patients with prolidase deficiency treated in our hospital. RESULTS: Of 21 patients (including the 2 mentioned above), 12 had a history of recurrent pulmonary infections and 10 were diagnosed as having chronic lung disease. Of seven chest CT scans performed, four patients had subpleural cysts, two patients had bronchiectatic changes, and one had diffused ground glass attenuation and minor linear atelectasis. Three patients died, with all deaths being attributed to respiratory insufficiency. CONCLUSIONS: Prolidase deficiency is frequently associated with various pulmonary manifestations, including extensive cystic changes that may be life endangering. The differential diagnosis of bilateral cystic changes should include prolidase deficiency, and pulmonary evaluation should be performed in patients with prolidase deficiency. Pediatr Pulmonol. 2016;51:1229-1233. © 2016 Wiley Periodicals, Inc.

Prolidase deficiency associated with systemic lupus erythematosus (SLE): single site experience and literature review.

INTRODUCTION: Prolidase deficiency (PD) is a rare autosomal recessive disorder which may have a wide spectrum of clinical features. These features include a characteristic facies, cognitive impairment, rashes or skin ulceration, splenomegaly, recurrent infections involving mainly the respiratory system, and iminodipeptiduria. The disorder is caused by a mutation in the PEPD gene. OBJECTIVE: To describe a cohort of unrelated PD patients from Northern Israel whose inborn error of metabolism was associated with systemic lupus erythematosus (SLE) and to identify in the medical literature all PD cases mimicked by and/or associated with SLE. METHODS: Three patients with PD associated with SLE were clinically, biochemically and genetically investigated. These patients were from 3 unrelated consanguineous families residing in Northern Israel. A computer-assisted (PubMed) search of the medical literature from 1975 to 2011 was performed using the following key words: Prolidase deficiency, SLE, and systemic lupus erythematosus. RESULTS: An association between PD and SLE was found in 10 PD patients. These 10 patients included three from our cohort of 23 PD patients, and seven out of just under 70 PD patients previously reported in the literature. CONCLUSION: The present findings underscore the relatively high incidence of the association between SLE and PD, suggesting that this association may not be coincidental. The phenotypic similarities between SLE and PD might suggest that the PEPD gene constitutes a modifier gene or a genetic risk factor in the causation of SLE.

Autosomal recessive renal proximal tubulopathy and hypercalciuria: a new syndrome.

BACKGROUND: The best described primary inherited proximal tubulopathies include X-linked hypercalciuric nephrolithiasis (XLHN), caused by a mutation in the chloride channel gene CLCN5, and classic Fanconi's syndrome, the genetic basis of which is unknown. The aim of this study is to examine the clinical, biochemical, and genetic characteristics of a highly consanguineous Druze family with autosomal recessive proximal tubulopathy and hypercalciuria (ARPTH), a syndrome not reported previously. METHODS: Three children (2 girls, 1 boy) of the family referred for evaluation of renal glycosuria and hypercalciuria and 10 of their close relatives were evaluated clinically and biochemically. All study participants underwent genetic analysis to exclude involvement of the CLCN5 gene. RESULTS: Evaluation of the 3 affected children showed glycosuria, generalized aminoaciduria, hypouricemia, uricosuria, low molecular weight (LMW) proteinuria, and hypercalciuria in all 3 children and phosphaturia in 2 children. They had no metabolic acidosis or renal insufficiency. One affected girl had nephrocalcinosis. Two children had a history of growth retardation and radiological findings of metabolic bone disease. Parathyroid hormone and 1,25-dihydroxyvitamin D [1,25(OH)2Vit D] blood levels in affected children were normal. Unaffected family members examined had no renal tubular defects or LMW proteinuria. Genetic linkage analysis excluded cosegregation of the ARPTH phenotype with the CLCN5 locus. CONCLUSION: ARPTH is a new syndrome characterized by nonacidotic proximal tubulopathy, hypercalciuria, metabolic bone disease, and growth retardation. It can be distinguished from XLHN by its autosomal recessive mode of inheritance and normal serum levels of calciotropic hormones, as well as the absence of LMW proteinuria in obligate carriers. The gene mutated in ARPTH remains to be identified.

MPGN type I induced by granulocyte colony stimulating factor.

We report a girl with severe congenital neutropenia who has received long-term granulocyte-colony stimulating factor (G-CSF) therapy and has developed macroscopic hematuria, proteinuria, and decreased renal function associated with biopsy-proven membranoproliferative glomerulonephritis (MPGN) type I. Temporary discontinuation of G-CSF therapy as well as the use of glycosylated G-CSF has resulted in improvement in renal manifestations. We postulate that the MPGN was G-CSF-induced. Long-term G-CSF therapy should be used with great caution and close surveillance of kidney function.