Şule Ünal

Focal Segmental Glomerulosclerosis Associated with Mitochondrial Cytopathy: Report of Two Cases with Special Emphasis on Podocytes

We report two children with focal segmental glomerulosclerosis (FSGS) associated with mitochondrial cytopathy (MC). Case 1 was diagnosed as MC with the findings of ptosis, ophthalmoplegia, failure to thrive, high serum lactate and pyruvate levels, ragged red fibers in muscle biopsy and the common 4.9 kb deletion in mtDNA when she was four years old. She subsequently developed FSGS four years later. Case 2 was a four month-old girl presenting with feeding difficulty from birth, with vomiting, seizures and nystagmoid eye movements, nephrotic proteinuria and hematuria. Renal biopsy revealed FSGS. Ultrastructural study demonstrated markedly pleomorphic mitochondria in podocytes with a severe effacement of foot processes. The analyses of muscle biopsy and skin fibroblasts for respiratory chain enzymes were found to be normal, while mitochondrial DNA analysis revealed the population of a single deleted mtDNA in the heteroplasmic state. The present cases illustrate FSGS as a rare renal complication of mitochondrial disease and provide further evidence of podocytes possessing abnormal mitochondria which may cause glomerular epithelial cell damage leading to glomerulosclerosis.

Atypical combined immunodeficiency due to Artemis defect: A case presenting as hyperimmunoglobulin M syndrome and with LGLL

SCID can be caused by various genetic mutations leading to distinctive phenotypes according to the presence of T, B and NK cells. Artemis is a gene encoded on chromosome 10p. The deficiency of this molecule causes an inability to repair DNA double strand breaks and is one of the causes of radiosensitive T-B-NK+ SCID. The syndrome usually presents with opportunistic infections in the first years of life that leads to death if not treated with stem cell transplantation. The spectrum of the disease can be wide because of the heterogeneity of the mutations. Herein we present an atypical SCID (CID) patient with Artemis defect mimicking hyper IgM syndrome. Our patient had high serum IgM with low IgG and IgA levels, lymphocytosis and recurrent infections, intractable diarrhea, growth retardation, systemic CMV infection and sclerosing cholangitis. He also developed large granular lymphocytic leukemia and survived until the age of 6.5 years.

Glucose‐6‐phosphate dehydrogenase deficiency in neonatal hyperbilirubinaemia: Hacettepe experıence

The aim of this study was to investigate the prevalence of glucose‐6‐phospate dehydrogenase (G6PD) deficiency in newborn infants with neonatal hyperbilirubinaemia and to compare the clinical features of G6PD‐deficient and G6PD‐normal newborn infants.

Heavy metal levels in patients with ineffective erythropoiesis

OBJECTIVES Iron is taken into enterocytes at the duodenum via apical divalent metal-ion transporter 1 protein. Besides iron, divalent metal-ion transporter 1 also transports other divalent metals. We aimed to investigate blood heavy metal levels in patients with ineffective erythropoiesis. METHODS Blood levels of heavy metals including Pb, Al, Cd, Cr, Co, Cu, and Zn were measured in patients with thalassemia major (TM), thalassemia intermedia (TI), congenital dyserythropoietic anemia (CDA), and age- and sex-matched healthy controls. RESULTS Blood samples were obtained from 68 patients (51 patients with TM, 8 with TI, 9 with CDA), and a control group that included 65 volunteers. Patients with TM were found to have lower Al, Pb, and Zn, and higher Cd levels compared with the control group. The patients treated with deferasirox were further analyzed and Pb and Zn levels were found lower compared with the control group. DISCUSSION Patients with TM had tendency to have elevated levels of plasma cadmium; however, the median level was not at a toxic level. Increased metal-ion transporter 1 activity may cause heavy metal accumulation, but deferasirox chelation may be protective against heavy metals besides iron.

The questioning for routine monthly monitoring of proteinuria in patients with β-thalassemia on deferasirox chelation

ABSTRACT Background: Iron chelation therapy is one of the mainstays of the management of the patients with β-thalassemia (BT) major. Deferasirox is an oral active iron chelating agent. Proteinuria is one of the potential renal adverse effects of deferasirox, and monthly follow-up for proteinuria is suggested by Food and Drug Administration and European Medicine Agency. Methods: We aimed to investigate the necessity for monthly monitoring for proteinuria among patients with BT on deferasirox. A retrospective laboratory and clinic data review was performed for patients with BT major or intermedia who were treated with deferasirox chelation therapy. All patients were monitored for proteinuria for every 3 or 4 weeks after the initiation of deferasirox with serum creatinine and spot urine protein/creatinine ratios. Results: The median follow-up time of the 37 (36 BT major and one BT intermedia) patients was 44 months. Seven patients (18.9%) developed significant proteinuria (ratio ≥0.8). Of the 1490 measurements, 12 tests (0.8%) were proteinuric. Urine proteinuria resolved in all of the patients during the follow-up. The risk of proteinuria was higher at ages below a cut-off point of 23 years (p = 0.019). Patients, who were on deferasirox at doses above a cut-off dose of 29 mg/kg/day, were found to have higher risk of proteinuria development (p = 0.004). Conclusion: Proteinuria resolves without any complication or major intervention according to our results. Potentially more risky groups (age below 23 years old and receivers above a dose of 29 mg/kg/day) might be suggested to be followed monthly, besides monitoring all of the patients.

Successful Outcome With Fludarabine-Based Conditioning Regimen for Hematopoietic Stem Cell Transplantation From Related Donor in Fanconi Anemia: A Single Center Experience From Turkey.

Fanconi anemia (FA) is a heterogeneous autosomal recessive (and rarely X linked) disorder, which is characterized by congenital malformations, progressive bone marrow failure, and predisposition to malignancies. Hematopoietic stem cell transplantation (HSCT) is the only definitive treatment for the hematological manifestations in FA.

Effects of blood transfusion on cytokine profile and pulmonary function in patients with thalassemia major.

Thalassemia major (TM) is characterized by abnormal hemoglobin synthesis, which results in decreased oxygen delivery to the tissues, ineffective erythropoiesis and iron overload. The purpose of this study was to find out the predominant type of lung mechanical abnormalities in TM patients, the prevalence of the change in pulmonary diffusing capacity and to search the association of cytokines with pulmonary function tests (PFTs).

Assessment of Peripheral Neuropathy in Patients with β-Thalassemia via Electrophysiological Study: Reevaluation in the Era of Iron Chelators

Abstract Peripheral neuropathy is one of the complications of β-thalassemia (β-thal) that has been investigated in limited reports. We aimed to detect the rate of peripheral neuropathy and risk factors for neuropathy development in patients with β-thal. The study was performed in patients with β-thal intermedia (β-TI) or β-thal major (β-TM). Prospective electrophysiological studies were achieved via standard procedures. A total of 27 patients were enrolled in the study. Electrophysiological studies for both motor and sensory nerves were within normal range. In motor nerve studies, delayed peroneal nerve latency was found in patients with high ferritin levels, increased ulnar nerve amplitude was detected in patients ≥20 years old, and increased tibial nerve amplitude was seen in patients with low copper levels. We could not show peripheral neuropathy in our patients. Increased ferritin level, older age, and copper deficiency may cause mild changes in electrophysiological studies of motor nerves.

The Hematological and Molecular Spectrum of α-Thalassemias in Turkey: The Hacettepe Experience.

Objective: The spectrum of α-thalassemias correlates well with the number of affected α-globin genes. Additionally, combinations of the several non-deletional types of mutations with a large trans deletion comprising the 2 α-globin genes have an impact on the clinical severity. The objective of this study was to analyze the hematological and molecular data of 35 patients with Hb H disease from a single center in order to identify the genotypes of Hb H disease and genotype-phenotype correlations. Materials and Methods: Herein, we report the hematological and mutational spectrum of patients with Hb H disease (n=35). Additionally, genotypes of α-gene mutations of 78 individuals, who were referred to our institution for α-gene screening, were analyzed. Results: Supporting the previous data from Turkey, -α3.7 was the most common mutation among patients with Hb H disease (62.8%) and in the other 78 subjects (39.7%). Of the patients with Hb H disease, the most common genotypes were -α3.7/--20.5, -α3.7/--26.5, and -α3.7/--17.5 in 10 (28.6%), 6 (17.1%), and 6 (17.1%) patients, respectively. Another small deletion, -4.2 alpha, and several non-deletional types of α-gene mutations, namely α (-5nt): IVS-I donor site (GAG.GTG.AGG->GAG.G-----); α (PA-2): AATAAA>AATGGA, and α (cd59): GGC->GAC, were found to be associated with Hb H disease when present at trans loci of one of the large deletions given above. The combinations consisting of 1 non-deletional and 1 of the large deletional types of mutations (αTα/--) at trans loci were found to result in a more severe phenotype compared to the genotypes composed of 1 small trans deletion of a large deletion (-α/--). The combination of α (Cd59) and -- in trans was associated with severe phenotype and the disease was associated with an increase in Hb Bart’s level with null Hb H. In spite of the presence of 2 intact α-globin genes, homozygosity for PA-2 mutation resulted in severe Hb H disease. Conclusion: This study indicated that Hb H disease is not rare in Turkey and its genotype is quite heterogeneous.

Diagnosis: Melanoderma after Hematopoietic Stem Cell Transplantation.

Figure 2. A) Skin. A slight perivascular infiltration of mononuclear inflammatory cells and dermal melanophages (arrows) are seen (HEx200). B) An increment in melanin pigment in basal keratinocytes (arrow heads) and dermal melanophages (white arrows) are highlighted by Fontana-Masson stain (x200). Figure 1. Patchy melanoderma lesions mimicking ecchymoses in the legs, trunk.