Nutcracker syndrome in pediatrics: initial findings and long-term follow-up results.

BACKGROUND: Nutcracker syndrome (NCS) describes a set of symptoms and signs resulting from compression of the left renal vein (LRV). There is a lack of knowledge about its natural course, diagnosis, and management, especially in children. Herein, we present our single-center experience with a large number of patients who have long-term follow-up results. METHODS: All patients with NCS diagnosed between January 2011 and March 2021 were included and their data were obtained retrospectively. RESULTS: A total of 123 NCS patients (85 females) were included. The median age at the time of diagnosis was 12 (IQR 10-14) years, and BMI percentiles were below 5% in 38% of the cases. At the time of diagnosis, two-thirds of the patients were asymptomatic. The most common laboratory finding was nephritic proteinuria (98%), followed by microscopic hematuria (16%). Signs of LRV compression were significantly more evident in upright position Doppler ultrasonography (DUS) examination. All patients have been followed conservatively; hematuria and/or proteinuria resolved in 43 of the 108 patients (40%) within 35.8 ± 25.8 months of follow-up. Control DUS was performed in 52 patients after a mean period of 39.1 ± 21.3 months. The median peak velocity and diameter ratios of the LRV in the upright position were found to be decreased significantly when compared to the initial assessment (p < 0.05). Normal DUS findings were noted in 13 patients at the final evaluation. CONCLUSIONS: In unexplained proteinuria and/or hematuria, NCS should be considered, especially in asthenic adolescents. Our results support conservative management in children as the first-line treatment approach.

Antenatal Hyperechogenic Colon and Cystinuria.

A male newborn was investigated for history of antenatal hyperechogenic colon (HEC) detected at 32 weeks of gestation. In the first week of life, urinary ultrasonography showed nephrolithiasis. Urinary amino acid analysis expressed increased excretion of dibasic amino acids, and high urinary cystine levels were detected in both spot and 24-hour urine specimens. He was diagnosed as cystinuria, and genetic analysis of the patient revealed a heterozygous mutation in SLC7A9 gene. Antenatal presentation of cystinuria with HEC is rare and reported to be associated with a more severe disease course.

Exertional leg pain represents a severe disease phenotype in childhood familial Mediterranean fever.

OBJECTIVES: Familial Mediterranean fever (FMF) is the most common monogenic autoinflammatory disease. Recurrent fever, serositis, and arthritis are common findings of the disease. In addition, musculoskeletal complaints such as exertional leg pain can be overlooked, although they are common and affect patients' quality of life. The aim of this study was to evaluate the frequency of exertional leg pain in pediatric FMF patients and to analyze the association of this finding with other characteristics of FMF. METHODS: The files of FMF patients were retrospectively evaluated. The clinical characteristics and disease severity of the patients with exertional leg pain were compared with the patients without exertional leg pain. International severity scoring system for FMF (ISSF) and Mor severity score were used for assessment. RESULTS: The study included 541 FMF patients (287 females), 149 (27.5%) with exertional leg pain. The median colchicine dosage was significantly higher in patients with exertional leg pain (p = 0.02), arthritis (p = 0.001) and arthralgia (p˂0.001) were encountered more frequently in the attacks of these patients. The median disease severity scores calculated by both Mor severity scale and ISSF were significantly higher in patients with exertional leg pain compared to those without (p˂0.001). In the group of patients with exertional leg pain, the M694V mutation, either in one allele or in two alleles, was found to be significantly more common (p = 0.006 and p˂0.001, respectively). CONCLUSIONS: Exertional leg pain in pediatric FMF patients is the component of moderate-to-severe disease course, and this may be considerably associated with the presence of M694V mutation.

Infantile systemic lupus erythematous presenting as nephrotic syndrome in a 12-month-old boy: a case report.

BACKGROUND: Systemic lupus erythematous (SLE) is extremely rare in infants and has been reported to be a much more severe disease with higher prevalence of critical organ involvement. Herein we present the clinical and laboratory features of infantile SLE (iSLE) with an onset of nephrotic syndrome (NS) during the first year of life. CASE: A 12-month-old boy was suffering from generalized edema for two months. He had thrombocytopenia, hemolytic anemia with positive direct and indirect Coombs tests and proteinuria of nephrotic-range. Other laboratory studies revealed slightly decreased C3, low C1q and normal ANA and C4 levels; anti-phospholipid and anti-cardiolipin antibodies were also found to be negative. Renal biopsy revealed Class IV lupus nephritis. The patient also suffered from massive pulmonary thromboembolism. Complete remission was achieved with steroid, cyclophosphamide, mycophenolate mofetil and anticoagulant therapy. CONCLUSION: iSLE should be kept in mind especially in infantile NS with multisystem involvement. Renal biopsy is mandatory for early diagnosis. Although the disease was reported to have poor prognosis, complete remission could be achieved with intensive immunosuppressive therapy.

Hb D-Los Angeles [beta121(GH4)Glu>Gln] and Hb Beograd [beta121(GH4)Glu>Val]: Implications for their laboratory diagnosis and genetic origins.

OBJECTIVE: The aim of this study was to determine the laboratory diagnosis and genetic origins of the hemoglobin (Hb) variants, Hb D-Los Angeles and Hb Beograd observed frequently in our region. MATERIAL AND METHODS: Hb variants were investigated in one Hb D-Los Angeles and two Hb Beograd families. These families were unrelated with each other. For the determination of Hb variants, alkaline/acid electrophoresis, HPLC, DE-52 micro-column chromatography procedures were applied. Mutations were determined by non-radioactive fluorescence automated DNA sequencing. Beta globin gene cluster haplotypes were identified by RFLP analysis at seven loci known as ε-Hinc II, Gγ-Hind III, AΨß-Hind III, 5'Ψß-Hinc II, 3'Ψß-Hinc II, ß-Ava II ve 3'ß-Hinf I. RESULTS: Three novel beta globin gene cluster haplotypes were identified as in relation with Hb D-Los Angeles [--+-+++], Hb Beograd [+----++ and -+-(+/-)(+/-)+(+/-)]. These haplotypes were reported for the first time in the world population Conclusion: In this study we emphasize the importance of DNA seqeuncing and other laboratory procedures for the identification of Hb variants in premarital diagnosis. On the other hand we discuss also the genetic origins of these Hb variants.

A review of abnormal hemoglobins in Turkey.

In this review, abnormal hemoglobins published in Turkish population during the last 4 years are presented. Further, analysis of the 88 abnormal hemoglobins is geven.

Serum amyloid A1 -13 T/C alleles in Turkish familial Mediterranean fever patients with and without amyloidosis.

Previously reported studies concerning the effect of homozygosity of the 1.1 allele of the SAA gene found a correlation between this haplotype and susceptibility to amyloidosis in FMF patients. Another report revealed a strong association between SAA1 -13T/C and secondary amyloidosis in the rheumatoid arthritis patient group. In this study, we aimed to determine the effect of SAA1 -13T/C in FMF patients with and without amyloidosis. The study cohort, consisting of 166 patients with FMF was divided into two groups, according to the presence (n=66) or absence (n=100) of renal amyloidosis at study entry. MEFV gene mutation analysis and allelic variant of SAA1 gene -13 T/C was analyzed according to the previously described techniques. SAA1 -13 T allele frequencies were 0.5816, 0.23 and 0.4242 in controls, FMF patients and FMF-amyloidosis patients respectively. The difference between controls vs. FMF patients and FMF-amyloidosis patients were 0.0002 and 0.1673 respectively. It was 0.0071 for FMF-patients vs. FMF-amyloidosis. When 694 M/V homozygous nonamyloid-FMF group was compared with 694 M/V carriers of the FMF-amyloidosis group, the difference was 0.049. When carrying TT allele was considered, the difference between controls vs. FMF patients and FMF-amyloidosis patients were 0.0001 and 0.58. It was 0.0003 for FMF patients vs. FMF-amyloidosis. When 694 M/V homozygous nonamyloid-FMF group was compared with 694 M/V carriers of the FMF-amyloidosis group, the difference was 0.03. Carrying SAA -13T in homozygote state revealed a 7.9 (95% CI 3.6 -17.5) fold risk for the occurrence of amyloidosis when compared with FMF patients without amyloidosis. This was 8.75 (95% CI 3.0 - 25.1) when 694 M/V homozygotes were taken into consideration. Our data revealed that the genotype SAA1 -13T has at least an effect on the development of amyloidosis. As more data on this polymorphism accumulate, we will understand its effect on the pathogenesis of amyloidosis in FMF.

Interleukin-6 (IL-6) -174 G/C polymorphism in familial Mediterranean fever patients with and without amyloidosis.

Familial Mediterranean fever (FMF) is a recessive disorder characterized by attacks of fever and inflammation. A sustained inflammatory reaction is observed in the disease course, and cytokine levels such as interleukin (IL)-1, IL-6 and tumor necrosis factor-alpha (TNF-alfa) are shown to increase during and between the attacks. In this study, we investigated the role of the functionally important IL-6 -174 G/C polymorphism in the clinical outcome of FMF and amyloidosis. One hundred and fifty-six FMF patients (80 with amyloidosis) and 90 healthy controls were studied. The genotype distributions and allele frequencies of the patients and the controls were found to be similar, and the differences between the groups were not statistically significant. The results show that IL-6 -174 G/C polymorphism is not associated with FMF and amyloidosis. The increase observed in cytokine levels during and between the attacks is more likely due to the inflammatory nature of the disease.

Factor V A4070G (His1299Arg) mutation in Turkish pediatric patients with thrombosis.

The role of the prothrombotic mutations in pediatric thrombosis are being investigated. Mutations in the factor V gene (FV G1691A and FV A4070G) leading to activated protein C resistance, the main pathological condition in thrombosis and prothrombotic mutations contributing to thrombosis have been identified. The aim of this study is to reveal the role of FV A4070G mutation in pediatric thrombosis. 314 patients with thrombosis at pediatric age including also 111 stroke patients and 127 healthy controls were included to the study. The FV A4070G mutation was evaluated independently and also the combined effects with other prothrombotic mutations were also investigated. In pediatric stroke group FV A4070G was found not to be a risk factor with an OR of 1.04 (CI 95%: 0.56-1.93, p= 0.884). Further studies are needed to study the role of FV A4070G with other risk factors belong to HR2 haplotype.

Serum amyloid A1 and tumor necrosis factor-alpha alleles in Turkish familial Mediterranean fever patients with and without amyloidosis.

The major complication of familial Mediterranean fever (FMF) is AA amyloidosis. The influence of FMF gene (MEFV) mutations and/or unknown environmental factors and other genetic modifiers are likely to affect the phenotypic variations of the disease and the development of amyloidosis. Serum amyloid A is a serum precursor of AA amyloid that is induced by inflammatory cytokines including TNF-alpha. Our analysis of SAA1.1 frequency in Turkish FMF-amyloidosis patients, revealed a higher frequency compared to non FMF-amyloidosis patients but the difference was not significant. On the other hand, the distribution of SAA1.1 homozygosity among FMF-amyloidosis patients was 55.5% compared to FMF-non-amyloidosis patients (30.8%) which was statistically significant revealing a 2.5 fold risk for the occurrence of amyloidosis. There was no significant difference between the controls and FMF patients with and without amyloidosis for the TNF-alpha-308 G-A allele. It is worth noting that all TNF-alpha-308 G-A carriers (n = 6) in FMF-amyloidosis group have SAA1.1 homozygosity compared to 2/11 in FMF-non-amyloidosis group. Further evaluation of these polymorphisms may have importance and need further study.

Effect of plasminogen activator inhibitor-1 4G/5G polymorphism in Turkish deep vein thromboembolic patients with and without prothrombin 20210 G-A.

Prothrombin 20210 G-A mutation is a common factor that predispose to thrombosis. The effect of the mutations in PAI-1 gene on the risk of thrombosis is controversial. We aimed to evaluate the role of these two polymorphisms in Turkish patients with deep vein thrombosis. Although there was no statistically significant difference in patient and control group for the distribution of PAI-1 4G/5G polymorphism in the present study, the risk of thrombosis increased from 3.4 fold to 8.4 in patients carrying PT20210 A and PAI-1 4G.

Coexistence of Two Prothrombotic Mutations, Factor V 1691 G-A and Prothrombin 20210 G-A, and the Risk of Thrombosis in Turkish Population.

This report summarizes the coexistence of two mutations; Factor V 1691 G-A and prothrombin 20210 G-A in Turkish population and emphasises on the point that, this coexistence increases the risk of thrombosis in such patients. In thrombophilia screening programs, these two variants should be included, particularly in Turkish population.

Homozygosity for the HR2 Haplotype: Is It a Risk Factor for Thrombosis?

A4070G (His 1299 Arg) polymorphism in exon 13 of factor V gene can influence factor V levels and contribute to the activated protein C resistance. We are presenting our data concerning Turkish population and postulate that homozygosity for the HR2 haplotype may be an important risk factor for thrombosis.

First Observation of Hemoglobin Pyrgos [ß83(EF7) Gly→Asp] in Turkish Population.

Hemoglobin Pyrgos [ß83 (EF7) Gly→Asp] is a rare hemoglobin variant. This report describes the first observation of this variant in an 18-year-old Turkish girl living in Isparta.

Further observation of Hemoglobin Beograd (B121 Glu-Val) in Turkish population.

Hemoglobin Beograd (B121 Glu-Val) is a rarely reported hemoglobin variant. It was first reported in Turkey in 1984. This report is a further observation of this variant in a 22-years old Turkish man.

First observation of homozygous hemoglobin hamadan (B 56 (D7) GLY-ARG) and beta thalassemia (-29 G>A)- hemoglobin Hamadan combination in a Turkish family.

During screening surveys for beta thalassemia and abnormal hemoglobins in Mugla, a city located in the Aegean Region of Turkey, a hemoglobin variant was detected in two large families residing in two neigboring cities (i.e., Mugla and Aydin) without any clinical signs. Further analysis of the variant revealed it as Hb Hamadan (B 56 (D7) GLY-ARG). Family screening revealed the father of the propositus as homozygote Hb Hamadan. The grandfather of the index case was detected as combination of Hb Hamadan with beta thalassemia. The beta thalassemia carrier had a promotor mutation at -29 G>A, which is also a novel mutation. Furthermore, we described a simple and rapid restriction enzyme digestion protocol (Hha I) for the verification of Hb Hamadan. The clinical and hematologic data of the index case and his father showed that neither homozygous Hb Hamadan nor combination with beta thalassemia has clinical importance. This is also important especially from the prenatal diagnosis point of view.