Pyruvate kinase deficiency in 29 Turkish patients with two novel intronic variants.

Pyruvate kinase (PK) is a key enzyme of anaerobic glycolysis. The genetic heterogeneity of PK deficiency (PKD) is high, and over 400 unique variants have been identified. Twenty-nine patients who had been diagnosed as PKD genetically in seven distinct paediatric haematology departments were evaluated. Fifteen of 23 patients (65.2%) had low PK levels. The PK:hexokinase ratio had 100% sensitivity for PKD diagnosis, superior to PK enzyme assay. Two novel intronic variants (c.695-1G>A and c.694+43C>T) have been described. PKD should be suspected in patients with chronic non-spherocytic haemolytic anaemia, even if enzyme levels are falsely normal. Total PKLR gene sequencing is necessary for the characterization of patients with PKD and for genetic counselling.

Abdominal pain in a 5-year-old girl with bilateral nephromegaly: Answers.

Renal involvement in non-Hodgkin lymphoma is a recognized development, but it mostly follows a diagnosis of lymphoma. We describe a rare case of a T-cell-type non-Hodgkin lymphoma that first presents as nephromegaly in a 5-year-old girl admitted to the emergency department with abdominal pain. Further investigation revealed bilateral nephromegaly, but the results of blood tests, imaging studies, and bone marrow aspiration were inconclusive. During the second week of hospitalization, significant physical examination revealed an enlarged lymph node in the anterior cervical chains, confirming a diagnosis of Non-Hodgkin's lymphoma. This case illustrates that it is important to have a high degree of suspicion in any patient presenting with unexplained enlarged kidneys without any identifiable cause because it could be the first presentation of a hematologic malignancy.

A Rare Cause of Neonatal Hemolytic Anemia: Glutathione Synthetase Deficiency.

BACKGROUND: Isolated hemolysis or hemolytic anemia and 5-oxoprolinuria are 2 distinct medical conditions in the clinical spectrum associated with glutathione synthetase deficiency. CLINICAL OBSERVATION: A 1-day-old female baby presented with anemia and respiratory distress. Her hemoglobin level was 9.5 g/dL and the total serum bilirubin level was 5.6 mg/dL. Metabolic acidosis was detected in her blood gas analysis. Metabolic acidosis recurred despite treatment and further investigation was required. Her 5-oxoproline level was 3815 mmol/mol creatinine in urine organic acid analysis, and a homozygous mutation [p.R125H (c.374G>A)] was found in the glutathione synthetase gene. CONCLUSIONS: GSD has been observed in very few patients and is rarely considered in the differential diagnosis of hemolytic anemia in newborns.

Congenital Hemophilia A Presenting With Hashimoto's Encephalopathy and Myocarditis: The First Reported Case.

Here, we report a case of hemophilia A with myocarditis, encephalopathy, and spontaneous intramedullary hemorrhage. A 14-month-old male infant presented with loss of consciousness, generalized tonic-clonic convulsions, and cardiac failure. The neurological examination was normal. Myocarditis was diagnosed. After administration of fresh frozen plasma, the aPTT did not return to normal. The factor VIII (FVIII) level was 10.2% the normal level, and the patient was diagnosed with hemophilia A. The cerebrospinal fluid (CSF) evaluation was unremarkable, with the exception of elevated CSF protein levels. An electroencephalogram revealed diffuse slowing of background activity. The spinal MRI revealed chronic bleeding in areas of the medulla spinalis. Tests for the antibodies associated with autoimmune encephalitis were negative. Anti-thyroglobulin (THG) (11.8 U/mL [normal, 0 to 4 U/mL]) and anti-thyroid peroxidase (TPO) (53.9 U/mL [normal, 0 to 9 U/mL]) antibodies were present in the serum. The patient received 1 g/kg intravenous immunoglobulin G (IVIG) for 2 days based on a diagnosis of myocarditis and Hashimoto's encephalopathy. After the first month of treatment his clinical findings were negative. He developed an inhibitor to FVIII 1 month after initiation of FVIII replacement therapy. Hemophilia A has various clinical presentations. Autoimmunity may lead to early inhibitor development in patients with hemophilia.

Incidence and clinical features of acute rheumatic fever in Kayseri, Central Anatolia, 1998-2011.

BACKGROUND: In developing countries, acute rheumatic fever is the most common cause of acquired heart disease in the paediatric and adolescent population. It is believed that vulnerability to developing acute rheumatic fever is associated with several factors such as socio-economic and living conditions. Aim Determine the incidence and clinical characteristics of acute rheumatic fever in the Central Anatolia region of Kayseri within the last 14 years, and to make a comparison of two 7-year periods. Material and methods We performed a retrospective analysis of 624 patients who were diagnosed with acute rheumatic fever at the Department of Pediatric Cardiology in the Medical Faculty of Erciyes University between January, 1998 and December, 2011. RESULTS: The mean age of patients was 10.9±2.7 years. The female/male ratio was 1.4. When patients were categorised according to age groups, the largest group represented 376 patients (60.3%) aged between 10 and 14 years. The estimated incidence rate of acute rheumatic fever was 7.4/100,000 in the Central Anatolia region of Kayseri. Among the major findings, the most common included carditis at 54%, arthritis at 35%, Sydenham's chorea at 25%, and subcutaneous nodules at 0.5%, respectively. No significant difference was found between the first 7-year period and second 7-year period in distributions of age, gender, and major findings. CONCLUSION: Although there has been socio-economic development in Turkey in the recent years, the incidence of acute rheumatic fever is still high in the Central Anatolia region of Kayseri.

Cryptococcal meningitis in a non-HIV patient with solid organ transplantation.

Cryptococcal meningitis (CM) is often associated with human immunodeficiency virus (HIV). Recently, this microorganism has been increasingly identified in HIV-negative patients. CM cases are encountered in HIV-negative individuals, especially secondary to liver disease, solid organ transplantation (SOT), tuberculosis, lymphoproliferative diseases with T-cell-mediated immunological disorders, long-term corticosteroid use, malignancies, diabetes mellitus, and sarcoidosis. Our patient is an HIV-negative, SOT case with CM. It should be considered that CM can also occur in HIV-negative patients. As in our case, patients receiving long-term immunosuppressive therapy should be evaluated for CM, and renal functions should be closely monitored during treatment. There is a need for more case reports on the subject, especially in CM detected HIV-negative patients, due to the different treatment protocols and challenging clinical conditions compared to HIV-positive cases.

Accidental intramuscular overdose administration of vincristine.

Vincristine (VCR) is a fundamental component of various chemotherapy protocols. Several reports of accidental intramuscular (i.m.) administration or overdose of VCR have been published in the medical literature. We report on an uneventful clinical course of both i.m. and overdose of VCR in a 6-year-old girl with Wilms' tumor. To prevent the administration of overdosed drug by the i.m. route accidentally, chemotherapy should be administrated only by experienced medical doctors.

Intracranial hemorrhage in children with congenital factor deficiencies.

BACKGROUND: Intracranial hemorrhage (ICH) is a life-threatening situation in childhood. Congenital factor deficiencies (CFD) like hemophilia may cause ICH, and ICH may be the initial presentation in some cases. METHODS: From 2000 to 2010, 107 children with CFD from Erciyes University, Faculty of Medicine, Department of Pediatric Hematology, were evaluated. The ICH episodes were identified by medical history, general physical examination, detailed neurological examination, and CT or MR scan. The management strategies, surgical intervention, and outcome were noted. RESULTS: Twenty-one episodes of ICH were seen in 18 patients (16.8%) out of 107 CFD patients. The mean age of the patients was 42.1 months. Fourteen out of 18 patients were male, and four were female. Twelve (57.1%) out of 21 ICH episodes were caused by trauma, and nine (42.9%) were non-trauma related. Epidural hematoma was most frequently observed. All patients survived, but four had decrease in intellectual capacity and motor deficit. CONCLUSION: The optimal management of ICH in children with CFD depends on immediate recognition and prompt replacement therapy to ensure hemostatic balance with adequate surgical intervention.

Evaluation of vertebral bone marrow fat content by chemical-shift MRI in osteoporosis.

OBJECTIVE: To quantitatively evaluate vertebral bone marrow fat content and investigate its association with osteoporosis with chemical-shift magnetic resonance imaging (CS-MRI). MATERIALS AND METHODS: Fifty-six female patients (age range 50-65 years) with varying bone mineral densities as documented with dual x-ray absorptiometry (DXA) were prospectively included in the study. According to the DXA results, the patients were grouped as normal bone density, osteopenic, or osteoporotic. In order to calculate fat content, the lumbar region was visualized in the sagittal plane by CS-MRI sequence. "Region of interest" (ROI)s were placed within L3 vertebral bodies and air (our reference point) at different time points by different radiologists. Fat content was calculated through "signal intensity (SI) suppression rate" and "SI Index". The quantitative values were compared statistically with those obtained from DXA examinations. Kruskal-Wallis, and Mann-Whitney U tests were used for comparisons between groups. The reliability of the measurements performed by two radiologists was evaluated with the "intraclass correlation coefficient". This study was approved by an institutional review board and all participants provided informed consent to participate in the study. RESULTS: Eighteen subjects with normal bone density (mean T score, 0.39 ± 1.3 [standard deviation]), 20 subjects with osteopenia (mean T score, -1.79 ± 0.38), and 18 subjects with osteoporosis (mean T score, -3 ± 0.5) were determined according to DXA results. The median age was 55.9 (age range 50-64 years) in the normal group, 55.5 (age range 50-64 years) in the osteopenic group, and 55.1 (age range 50-65 years) in the osteoporotic group (p = 0.872). In the CS-MRI examination, the values of "SI suppression ratio" and "SI Index" (median [min:max]) were calculated by the first and second reader, independently. There was no statistically significant difference between the groups with regard to vertebral bone marrow fat content (p > 0.05). According to the "intraclass correlation coefficient", the measurements were reliable (0.55 and 0.60). CONCLUSIONS: Vertebral bone marrow fat content calculated with CS-MRI is not a reliable parameter for predicting bone mineral density in female patients aged between 50 and 65 years.

Novel MTTP Gene Mutation in a Case of Abetalipoproteinemia with Central Hypothyroidism

Abetalipoproteinaemia (ABL) is an autosomal recessive disorder characterized by very low plasma concentrations of total cholesterol and triglyceride (TG). It results from mutations in the gene encoding microsomal TG transfer protein (MTTP). A nine-month-old girl was admitted to hospital because of fever, cough, diarrhea and failure to thrive. She had low cholesterol and TG levels according to her age. The peripheral blood smear revealed acanthocytosis. Thyroid function test showed central hypothyroidism. Cranial magnetic resonance imaging revealed the retardation of myelination and pituitary gland height was 1.7 mm. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene. Vitamins A, D, E, and K and levothyroxine were started. The coexistence of ABL and central hypothyroidism has not previously been reported. A homozygous novel mutation [c.506A>T (p.D169V)] was detected in the MTTP gene.

A case of congenital afibrinogenemia complicated with thromboembolic events that required repeated amputations.

Although congenital afibrinogenemia is a rare autosomal recessive bleeding disorder, it can be more frequently encountered in countries where consanguineous marriages are common. Congenital afibrinogenemia is characterized by the undetectable low level of fibrinogen, which causes hemorrhagic diathesis. Paradoxically, arterial and venous thromboembolic complications can develop in patients with afibrinogenemia, which may cause a diagnostic problem to anyone unfamiliar with its clinical features. We report a case of congenital afibrinogenemia presenting with bilateral ischemic lesions of bilateral foot and ankle that required amputations. The patient was treated with fibrinogen concentrate, low-molecular-weight heparin, aspirin, and nifedipine. In conclusion, arterial and venous thromboembolic complications are rare, but severe complications of afibrinogenemia. The management of thromboembolic complications in patients with afibrinogenemia is a balance game. At one end of the scale, there is a bleeding disorder, and at the other end, there is a thrombosis. This fine adjustment is a job of mastery.

Testicular adrenal rest tumors in patients with congenital adrenal hyperplasia.

OBJECTIVE: Early diagnosis and treatment of testicular adrenal rest tumors (TART) is important for gonadal functions and fertility protection in boys with congenital adrenal hyperplasia (CAH). In this descriptive study, we investigated the prevalence of TART in boys with 21-hydroxylase deficient (21OHD) CAH followed in our pediatric endocrine clinic. METHODS: The study group consisted of 14 male patients with a mean age of 9.6 ± 5.1 (range: 0.8-18.3) years. Six (42.9%) of the 14 patients were diagnosed as having salt-wasting type (SW) and eight (57.1%) patients - as having the simple virilizing (SV) form of 21OHD. Mean age at diagnosis was 2.9 ± 2.7 (range: 0.03-6.3) years. Two different radiologists performed scrotal ultrasonography. Chronological age, bone age, and anthropometric measurements were evaluated. Serum adrenocorticotropic hormone (ACTH), 17-alpha-hydroxyprogesterone (17OHP) and androstenedione levels were also evaluated in all patients during the follow-up period. RESULTS: Scrotal ultrasonography revealed bilateral TART in two patients (14.3%) and testicular microlithiasis (TM) in four patients (28.6%). One patient had both TART and TM bilaterally. During the follow-up period, the mean serum adrenocorticotropic hormone, 17OHP and androstenedione levels in the total group of patients were 130.0 ± 179.1 pg/mL (21.7-726.5), 5.8 ± 3.3 ng/mL (0.8-11.4) and 4.3 ± 4.1 (0.2-11.0) ng/mL, respectively. CONCLUSIONS: Microlithiasis or TART may be frequently encountered during the follow-up of patients with CAH. In order to prevent late complications including infertility, we suggest that ultrasonographic evaluations be performed yearly in all male CAH patients.