A Case of Congenital Adrenal Hyperplasia due to 3-Beta-Hydroxysteroid Dehydrogenase Deficiency Presented With Acute Liver Failure

Congenital adrenal hyperplasia (CAH) is a group of rare autosomal disorders characterized by a variety of defects in adrenal steroidogenesis. Most cases of CAH are due to an enzyme deficiency in either 21-hydroxylase or 11-beta-hydroxylase. A much rarer form of CAH due to 3-betahydroxysteroid dehydrogenase (3B-HSD) deficiency results in impaired synthesis of all steroid hormones. The clinical presentation of undervirilization in 46 XY patients, hyponatremia, hyperkalemia, and recurrent hypoglycemia in 3B-HSD deficiency cases is well described in the literature. We describe a neonate with 3B-HSD deficiency that presented with ambiguous genitalia and hypoglycemia and was found to have comorbid coagulopathy, cholestasis, and direct hyperbilirubinemia with liver failure that resolved with glucocorticoid and mineralocorticoid treatment. Prompt recognition of this disease is imperative for timely intervention.

Evaluation of a Custom SNP Panel for Identifying and Rectifying of Misjudged Paternity in Deficiency Cases

Parentage testing is routinely performed by genotyping short tandem repeat (STR) through capillary electrophoresis in the present. However, ambiguous or even misjudged paternity based on STRs happens from time to time in cases where only one putative parent is available. We analyzed STR data of 7,818,969 unrelated pairs and 75 close-relative pairs and found that although the probability of a random false match between non-relatives was 4.22 × 10–6, the incidence of false or ambiguous paternity results between children and first-degree relatives of their true parent was as high as 18.67%. These results highlight the risk of false inclusion of a relative or even non-relatives in parentage testing with STRs. We then validated all ambiguous STR results by targeted sequencing with a custom panel containing 4,830 individual identification single nucleotide polymorphisms (IISNP), found that the ratio of mismatch loci to total SNPs was 1.78–6.95% in close relatives compared with 10.93–13.49% in unrelated pairs. Last, we reported three real cases with undetermined paternity by STRs and rectified them by dissecting with our IISNP panel. These results suggested that high-density IISNP panel can be used to identify and rectify misjudged cases effectively.

Pyruvate Kinase Deficiency Cases Mimicking Congenital Dyserythropoietic Anemia

Introduction Pyruvate kinase (PK) deficiency is the most common glycolytic pathway defect that leads to hereditary hemolytic anemia with autosomal recessive inheritance pattern, which may present with severe hemolysis in the neonatal period, frequent blood transfusion requirement during infancy or with milder course of anemia. The prevalence reported among the Caucasians is 51 per million. Herein we present two cases of PK deficiency who were clinically and morphologically mimicking congenital dyserythropoietic anemia (CDA) at presentation and were diagnosed molecularly. Case 1 A three-year-old male patient was admitted with jaundice. Personal history revealed that he was born prematurely from a non-consanguineous family, and he did not need phototherapy at neonatal period. By the third month, he received first erythrocyte transfusion; then he needed transfusions every month. Strikingly, transfusion requirements increased in febrile episodes. Physical examination at admission revealed jaundice and splenomegaly. Complete blood count showed hemoglobin (Hb) 7.2 g/dL, mean corpuscular volume (MCV) 86.1 fL, mean corpuscular hemoglobin (MCH) 27.3 pg, mean corpuscular hemoglobin concentration (MCHC) 31.7 pg, and reticulocytes 12.3%. A blood film examination showed macrocytosis, hypochromia, anisocytosis, and rare spherocytes. Hemoglobin electrophoresis was normal, and direct Coombs' test was negative. The PK enzyme level was ignored since the patient was regularly transfused. Bone marrow aspiration showed erythroid hyperactivity and severe megaloblastic changes with double and multi-nucleated erythroid precursors suggestive for CDA. However, no genetic mutation detected concerning CDA (C15orf41, F8, F9, KLF1, CDAN1, VWF, SEC23B, GATA1, G6IBA genes). After negative molecular testing for CDA, sequencing of the PK-LR gene revealed the presence of a homozygous c.1151C> T mutation. Case 2 A three-month-old male patient presented with pallor and jaundice. Personal history revealed that he was born at term from a non-consanguineous family, and he required phototherapy and exchange transfusion due to icterus and anemia at the neonatal period. He needed erythrocyte transfusions during follow-up. Hemogram revealed Hb 6.7 g/dL, MCV 81.2 fL, MCH 25.2 pg, MCHC 31.1 pg, and reticulocytes 2.6%. Blood film examination showed polychromasia, rare spherocytes, and acanthocytes. Direct Coombs' test and Parvovirus B19 PCR analysis were negative. Bone marrow aspiration showed erythroid hyperactivity along with double and multi-nucleated erythroid precursors, which suggested CDA. However, no genetic mutation detected concerning CDA (SEC23B, CDAN1). The PK enzyme level was normal, which was 2 ½ months after the last transfusion. Finally, the molecular analysis of the PK-LR gene revealed the presence of a novel homozygous c.880G>A mutation. The mutation predicted as possibly damaging by in Silico analysis. Discussion The diagnostic approach to transfusion-dependent hereditary hemolytic anemia could be challenging related to false normal erythrocyte enzyme studies and osmotic fragility tests in previously transfused patients. It was reported that PK deficiency cases with inappropriately low reticulocytes might mimic CDA, which was discerned in cases where NGS performed for CDA but revealed PK-LR mutation. PK deficiency may lead to ineffective erythropoiesis due to erythrocyte ATP depletion, as well as CDA-like morphological findings (Cases 1 and 2) and low reticulocyte counts (Case 2). We suggest that in cases where CDA is suspected, PK deficiency should be considered in the differential diagnosis. Furthermore, instead of the PK enzyme level in patients with regular transfusions, PK-LR genetic analysis would be appropriate. Disclosures No relevant conflicts of interest to declare.

Spectrum Sensing in Cognitive Radio by Use of Volume-Based Method

Spectrum sensing is the mission of finding the licensed user signal situation, i.e. to determine the existence and deficiency of primary (licensed) user signal, the recent publications random matrix theory algorithms performs better-quality in spectrum sensing. The RMT fundamental nature is to make use of the distributed extremal eigenvalues of the arrived signal sample covariance matrix (SMC), specifically, Tracy-Widom (TW) distribution which is useful to certain extent in spectrum sensing but demanding for numerical evaluations because there is absence of closed-form expression in it. The sample covariance matrix determinant is designed for two novel volume-based detectors or signal existence and deficiency cases are differentiated by using volume. Under the Gaussian noise postulation one of the detectors theoretical decision thresholds is perfectly calculated by using Random matrix theory. The volume-based detectors efficiency is shown in simulation results.

Influence of androgen deficiency on carbohydrate metabolism in men

The article provides an overview of the current literature integrating clinical data on the role of androgen deficiency in pathogenesis of metabolic malfunctions and diabetes mellitus. The combination of androgen deficiency and diabetes mellitus is a risk factor of cardiovascular diseases. Due to the fact that general physicians, endocrinologist dont have knowledge of this problem most of androgen deficiency cases are not only remained without treatment but also not revealed.

Biofortification of Wheat with Iron

In various micronutrient-deficient countries, wheat is used as staple food, comprise more than 50% of the diet. Like many staple foods, wheat contain low concentration of iron (Fe). About two billion people globally have iron deficiency, especially in the regions where staple foods are based on cereal crops such as wheat. Because of high rate of Fe deficiency cases, increased Fe intake through staple food has become the main focused research area globally. As wheat is main source of protein and dietary energy for human beings, its potential to support reducing malnutrition related to Fe can be increased through producing genetically modified wheat varieties with high concentration of Fe. High Fe concentration in cereal crop is a major challenge. Even though during wheat is commonly fortify, promising and more long term solution is biofortification of wheat, which bases on the production of new wheat varieties with characteristically higher concentration of iron. Till now, may researches, which focused on increasing Fe in wheat, aimed at producing natural varieties in progenitor or related species. This review focused on the promising and sustainable approaching to maintain the improve concentration of iron in wheat.

Impact of Rare Bleeding Disorders during Pregnancy on Maternal and Fetal Outcomes: Review of 29 Pregnancies at a Single Center

Objective This study aims to give information about the relationship between different types of factor deficiencies and maternal/obstetric outcomes. Methods We retrospectively reviewed the medical records of eight women with factor deficiency disorders. The demographic and clinical features of the patients after their last pregnancies were registered retrospectively. Results There were 29 pregnancies among the 8 patients. The spontaneous abortion rate was relatively high in two patients with factor XIII deficiency (80% and 57.1%) compared with the other factor deficiency groups. There were 16 births, which included 1 set of twins, and 2 deaths (1 stillbirth and 1 postpartum exitus occurred in the same patient). Intrauterine growth restriction was noted in five cases; four of these occurred in factor X deficiency cases. The mean decrease in hemoglobin level of all patients after birth was 1.7 g/dL (range, 0.2–3.6 g/dL). Red blood cell transfusion was required only in one case of factor XIII deficiency. Conclusions There is currently no consensus on the pregnancy management of women with factor deficiencies because of the limited knowledge due to the rarity of such disorders. Labor should be managed in a dedicated unit with a team consisting of an obstetrician, a hematologist, an anesthesiologist, a midwife, and a pediatrician to minimalize the complications.