Elsevier

The Journal of Pediatrics

Volume 143, Issue 5, November 2003, Pages 658-661
The Journal of Pediatrics

Prevalence and significance of mutations in the familial Mediterranean fever gene in Henoch-Schönlein purpura

https://doi.org/10.1067/S0022-3476(03)00502-XGet rights and content

Abstract

Objectives

Based on the fact that Henoch-Schönlein purpura (HSP) occurs in approximately 5% of persons with familial Mediterranean fever (FMF), we assessed the prevalence and significance of FMF gene mutations in children with one or more episodes of HSP.

Study design

Thirty-four boys and 18 girls treated for HSP at Rambam Medical Center were interviewed and asked to donate blood. Mean age at disease onset was 6.7±2. 4 years, and mean follow-up was 3.8±1.3 years. Six predominant mutations (M694V, M680I, M694I, V726A, K695R, E148Q) in the MEFV gene were studied.

Results

Nine heterozygotes, three homozygotes and two compound heterozygotes, were identified. Altogether, five persons (10%) carried two mutated MEFV alleles, a number significantly exceeding that determined for the general Israeli population (1%–2%). Of these, three displayed genotypes associated with a mild form of disease (M694V/E148Q and V726A/V726A), and two had genotypes normally observed in disease-free persons (E148Q/K695R and E148Q/ E148Q).

Conclusions

Occult FMF cases much more numerous than expected were identified among children presenting with HSP. Such children should be closely monitored for renal complications, and treatment with colchicine should be considered.

Section snippets

Subjects

We obtained from the hospital's register the medical histories of 125 children with HSP treated at Rambam Medical Center (Haifa, Israel) between 1986 and 2001. Patients were classified as having HSP if they fulfilled three or more of the criteria proposed by Michel et al33: (1) palpable purpura involving mainly the lower extremities, (2) bowel angina, (3) gastrointestinal bleeding, (4) hematuria (gross or microhematuria), (5) age of onset <20 years, and (6) no previous history of medications

Results

The study group consisted of 52 patients with HSP (34 male patients, 18 female patients), of whom 30 were Arabs and 22 were Jews (Table II). The main demographic and clinical data are shown in Table II. The male:female ratio was 1.9. The mean age at disease onset was 6.7±2.4. Other than purpura, manifested by all patients, joint and gastrointestinal manifestations were especially frequent. Allele and genotype frequencies are shown in Table III Five patients had two mutated alleles, and nine had

Discussion

The frequency of the association between FMF and HSP, the causal relationship of which remains unclear, has been reported extensively.21., 22., 23., 24., 25., 26., 27., 28. In this study, we identified pyrin/marenostrin mutations in several patients with HSP who did not meet the clinical criteria for FMF. Five persons carried two FMF alleles, and nine had one MEFV mutation. Altogether, 19 of the 104 chromosomes studied (1:5.5) bore an MEFV mutation. Most importantly, 10% of our study cohort

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