Phenotype-genotype updates from familial Mediterranean fever database registry of Mansoura University Children' Hospital, Mansoura, Egypt.

BACKGROUND: Familial Mediterranean fever (FMF) is autosomal recessive disease that affects people from Mediterranean region, Europe and Japan. Its gene (Mediterranean fever [MEFV]) has more than 100 mostly non‑sense mutations. OBJECTIVES: The objective of the following study is to provide some phenotype‑genotype correlates in FMF by categorizing the Egyptian FMF cases from Delta governorates after analysis of the four most common mutations of MEFV gene (M680I, M694I, M694V, V726A). SUBJECTS AND METHODS: Clinically, suspected FMF cases using Tel‑Hashomer criteria were enrolled in the study. Cases were referred to Mansoura University Children’s Hospital that serves most of the most middle Delta governorates, in the period from 2006 to 2011. Subjects included 282 males and 144 females, mean age of onset 9.3 ± 2.2 years. All cases were analyzed for these mutations using amplification refractory mutation system based on the polymerase chain reaction technique. Five FMF patients agreed to undergo renal biopsy to check for development of amyloidosis. Analysis of data was carried out using SPSS (SPSS, Inc., Chicago, IL, USA). RESULTS: Mutation was found in 521 out of 852 studies alleles, the most frequent is M694V (35.4%) followed by M694I, V726A and M680I. 11 cases were homozygous; 7 M694V, 3 M680I and only one M694I case. Severe abdominal pain occurred in 31 (7.28%) but severe arthritis in 103 cases (24.2%). Strong association was found between arthritis and homozygous mutant compared with single and double heterozygous (72.7% vs. 33.3% and 20.24%, P < 0.001). Four amyloid cases were M694V positive. CONCLUSION: M694V allele is the most common among Egyptian FMF especially those with amyloidosis. We recommend routine check for amyloidosis in FMF cases to statistically validate this link.

A Recent Experience in an Egyptian Medical Center: Strategies for the Clinical and Genetic Diagnoses of Nephropathic Cystinosis.

Aims: To screen cases of infantile cystinosis among different forms of proximal renal tubular acidosis (RTA). Study Design: Cross sectional. Place and Duration of Study: From a total of 25 families of RTA followed up in Nephrology unit of Mansoura University Children's Hospital (MUCH), Egypt, two unrelated families were diagnosed as infantile nephropathic cystinosis using clinical suspicion plus mutation analysis of CTNS gene in the period between January 2008 and November 2012. Methodology: Two families with multiple cases of infantile nephropathic cystinosis have been diagnosed. In absence of high-performance liquid chromatography and tandem mass spectrometry used for measuring intraleucocyte cystine, diagnostic tools for cystinosis used in the current work were clinical and laboratory evidences of PRTA, slit lamp detection of corneal cystine crystals and finally identification of CTNS gene mutations. All patients were subjected to routine echocardiography because of accidental discovery of heart malformation in one case. Rare mutant variant of the first family was subjected to RNA analysis which unfortunately failed, alternatively an in silico study was used to predict splice site. Results: All patients with cystinosis manifested a severe clinical course. Proband of family 1 showed two known mutations; deletion in the exon 3 (c.18_21 del GACT) and substitution in acceptor splice site of intron 11 (c.971 -12G>A). In silico study predicted an anticipated splice site that modified the open reading frame in carboxy-terminal region. Probands of family 2 were affected by ventricular and atrial septal defects in younger, and mild mitral and aortic incompetence in older patient; their DNA analysis revealed a novel nonsense mutation (c.734 G>A) which caused a premature stop codon in position 245 of protein. Conclusion: Nephropathic cystinosis has been diagnosed with ease in Egyptian population without need of sophisticated investigations. A novel mutation had been added to the list of CTNS gene variants.

Endothelin-1 and leptin as markers of intrauterine growth restriction.

Objective. To explore the role of endothelin-1 (ET-1) and leptin in intrauterine growth restriction (IUGR) among preeclamptic and non-pre-eclamptic women. Methods. Forty three patients with a pregnancy complicated by IUGR, 23 cases with severe pre-eclampsia and 20 cases of non-pre-eclamptic were enrolled. Control group comprised 15 cases with uncomplicated pregnancy. Blood samples from umbilical artery and maternal venous blood were collected at the time of delivery for analysis of ET-1 and leptin levels. Mode of delivery, birth weight and Apgar score were also recorded. Results. The mean maternal and fetal ET-1 level was significantly higher in pregnancies complicated by IUGR than in control group. The mean maternal leptin level was significantly higher in pre-eclamptic patients when compared to nonpreeclamptic and control groups. Mean fetal leptin level was significantly lower in patients compared to control; however, when fetal leptin corrected to fetal weight, it was insignificantly different in the both groups. Conclusion. Maternal plasma ET-1 and leptin correlate with the degree of fetal growth restriction originating from deterioration of placental function. Maternal plasma leptin and ET-1 levels may reflect deterioration in fetal growth.

Correlation of thyroid and growth hormones to chromosomal instability in Egyptian Fanconi anemia patients.

OBJECTIVE: Fanconi anemia (FA) is a rare inherited genomic instability syndrome and usually associated with endocrine dysfunctions. We aimed to assess the diagnostic standards of chromosomal instability in FA and to correlate the breakage frequency with the severity of endocrinal dysfunctions. METHODS: Twenty seven FA patients were randomly selected from Hematology Unit of Mansoura University Children's Hospital; their mean age 8.8 yr. Sixteen normal children matched for age and sex were used as controls. Cytogenetic studies included peripheral blood lymphocyte cultures using phytohemagglutinin to obtain chromosomal spreads. Chromosomal breakage was induced by (i) Diepoxybutane 0.1 mug/ml. (ii) Mitomycin C 0.1 microg/ml. (iii) Irradiation of cultures to four radiation doses; 75, 150, 300 and 400 rads (rad1, rad2, rad3 and rad4 respectively). Chromosomal aberrations were scored from the previous 6 cultures besides a culture for spontaneous chromosomal breakage; then mean chromosomal breakage was calculated for the seven cultures. Endocrinal evaluation included quantitative determination of thyroid stimulating hormone (TSH) and tetraiodothyronine (T4), serum growth hormone (GH), insulin like growth factor-1 (IGF-1) and insulin levels. RESULTS: Chromosomal breakage was found to be significantly higher in patients than control when induced by Diepoxybutane (p = 0.003), Mitomycin (p = 0.001), rad3 (p = 0.043) and rad4 (p = 0.001). Mean chromosomal breakage was significantly negative correlated to head circumference (r = -0.57) and GH level (r = -0.50), with no significant correlation to other hormonal parameters. Mitomycin and rad4 were found more accurate than DEB test for diagnosis of FA in suspected cases. CONCLUSION: Correction of the frequently associated hormonal dysfunction (reduced GH and T4) should be considered in the treatment discipline of FA patients to improve their final height.

Impact of long-term oral iron supplementation in breast-fed infants.

OBJECTIVE: To weigh benefits of oral iron supplements on infant's growth against its potential hazards. METHODS: 248 exclusively breast-fed infants aged 4-6 months were consecutively enrolled and divided into treatment group given iron containing multivitamin (TG = 198) and control group (placebo, PG = 50) given the same multivitamin but without is subdivided according to clinical assessment into group A (well nourished) and group B (malnourished); both were further stratified according to basal blood iron status. Assessment was done after 6 and 12 months with concurrent collection of morbidity parameters (diarrhea and fever). Data were normalized and analyzed using SPSS and Eurogrowth softwares. RESULTS: After 6 months treatment, weight and length gain was better in TG compared to placebo especially evident in anemic malnourished infants (P 0.05). Morbidity risk was linked to immunologic background of infant; odds ratio for diarrhea and fever was higher in malnourished compared to well nourished (P 0.05) or iron therapy (P for well-nourished non-anemic treatment vs PG > 0.05). CONCLUSION: Oral iron supplementation resulted in better effects on growth velocity of breast fed infants especially those who were initially malnourished and anemic or at least iron depleted, with less marked morbidity than in iron replete infants.