Clinical and hematological features of homozygous hemoglobin O‐Arab [beta 121 Glu → Lys]

Hemoglobin O‐Arab [Beta 121 Glu → Lys] (Hb O‐Arab) is a rare abnormal hemoglobin (Hb) whose clinical and hematological features have been described in adults but not in children. We report three children, 9, 12, and 36 months of age, with homozygous Hb O‐Arab and assess the value of supplementary folic acid as treatment. Pediatr Blood Cancer 2013; 60: 506–507. © 2012 Wiley Periodicals, Inc.     

A case of X-linked α-thalassemia/mental retardation syndrome: Analysis of hemoglobin by an automated glycated hemoglobin analyzer

A 5-year-old male patient with X-linked α-thalassemia/mental retardation syndrome is reported. He showed multiple minor anomalies including characteristic facial abnormalities, α-thalassemia, severe mental retardation, and hypogonadism. Analysis of his hemoglobin by high performance liquid chromatography using an automated glycated hemoglobin analyzer revealed an abnormal peak. Identification of an abnormal peak by an automated glycated hemoglobin analyzer will aid in the diagnosis of patients with X-linked α-thalassemia/mental retardation syndrome.     

The diagnostic dilemma of congenital unstable hemoglobinopathies

Unstable hemoglobin variants represent a rare etiology of congenital hemolytic anemia. Without a high index of suspicion, plus proper laboratory testing and interpretation, the correct diagnosis can be elusive. We report on five children who were initially thought to have other congenital disorders such as hereditary spherocytosis or thalassemia, before β‐globin gene sequencing led to the definitive diagnosis. Recognizing the variable clinical presentation and laboratory data reported will aid clinicians in diagnosis of unstable hemoglobins variants in children with atypical forms of hemolytic anemia, particularly those with low pulse oximetry values or whose hemoglobin electrophoresis suggest β‐thalassemia trait. Pediatr Blood Cancer. 2010;55:1393–1395. © 2010 Wiley‐Liss, Inc.     

Anaphylaxis – Lessons learnt when East meets West

The rapidly increasing prevalence of allergic disorders over the past 2 decades highlights the need to understand the epidemiology of anaphylaxis. In Europe, the United States, and Australia, the incidence of anaphylaxis is estimated to be between 60 and 950 cases per 100 000 population, with a lifetime prevalence of anaphylaxis of 0.05%‐2%. The incidence appears to be increasing over time. Although the existing Asian literature is heterogeneous and limited by under‐reporting, it also suggests a similar increasing trend in anaphylaxis incidence in Asia. Anaphylaxis triggers in Asia, such as the predominance of shellfish and wheat in older children and adolescents, differ from those seen in Western populations. Triggers unique to Asia such as traditional Chinese medications, galacto‐oligosaccharides, and food delicacies have also been reported. Low usage of adrenaline as first‐line treatment of anaphylaxis is evident across all countries and is particularly concerning. There is a need to establish prospective, standardized protocols for anaphylaxis data collection and reporting, to enhance the collective understanding of anaphylaxis and its burden, gaps in management and to identify areas for future research and intervention in each region. Understanding of the underlying reasons explaining the difference between East and West will facilitate future primary preventive strategies.     

Hemolytic anemia due to hemoglobin Evans in an Argentinean family

Unstable hemoglobins are structural variants of the hemoglobin molecule, mostly originated by single amino-acid replacement in some globin chains. These changes affect molecule stability, leading to loss of solubility, precipitation, and cellular lysis. Patients carrying these unstable hemoglobins may present mild to severe chronic hemolytic anemia. Hemoglobin Evans is an unstable variant originated by replacement of valine with methionine at position 62 of the α-globin chain. We have identified this variant in a girl with an acute hemolytic crisis associated to pharyngitis, as well as in two of her family members. This is the third case of hemolytic anemia due to hemoglobin Evans reported in the literature.     

Differing phenotypes of Moyamoya disease in a familial case involving heterozygous c.14429G > A variant in RNF213

Moyamoya disease (MMD) is a chronic steno‐occlusive arteriopathy involving the development of abnormal collateral vessels. Ring finger protein (RNF213) on the 17q25.3 locus was identified as an MMD‐susceptibility gene in East Asian populations. We report a 5‐year‐old Japanese boy diagnosed with cerebral infarction and unilateral MMD. Magnetic resonance angiography (MRA) showed severe stenosis of the left internal carotid artery (ICA), terminal portion of the left ICA, and left origin of the posterior cerebral artery. Genetic testing indicated a heterozygous c.14429G > A (formerly described as c.14576G > A) variant in RNF213. The boy's mother had no neurological symptoms, but sequencing of RNF213 showed the same variant, and MRA indicated stenosis of the terminal bilateral ICA. This is the first report, to our knowledge, of different MMD phenotypes in a familial case involving the same heterozygous c.14429G > A variant in RNF213. Genetic testing for RNF213 is suggested for family member screening.     

Hydroxyurea treatment of children with hemoglobin SC disease

The efficacy of hydroxyurea in hemoglobin SC (HbSC) patients is not well documented. We describe the long‐term response to hydroxyurea in children with clinically severe HbSC. In 15 patients, hydroxyurea resulted in a significant increase in mean corpuscular volume (MCV) and fetal hemoglobin (HbF) and a significant decrease in episodes of acute chest syndrome and hospitalization for pain; there was no effect on hemoglobin level. The most significant side effect was thrombocytopenia, which led to discontinuation of treatment in one patient. This study suggests that hydroxyurea has efficacy and is safe for long‐term therapy in patients with HbSC. Pediatr Blood Cancer 2013;60:323–325. © 2012 Wiley Periodicals, Inc.     

Predictive factors for survival for out‐born infants born between 23 and 24 weeks of gestation in the post‐surfactant era: Fourteen years’ experience in a single neonatal care unit, 1987–2000

Background: The purpose of the present paper was to identify the predictive factors for survival for out‐born infants born between 23 and 24 weeks of gestation. Methods: Ninety‐two infants born between 23 and 24 weeks’ gestation who were admitted to a level III neonatal intensive care unit from 1987 to 2000, were retrospectively studied. Survival was defined as discharge from the neonatal intensive care unit. Logistic regression was done to determine which clinical factors were most predictive of survival. The independent variables that were entered into the models were determined by preliminary univariate analysis. Results: Ninety‐two infants were enrolled in the present study, 49 of whom survived in the surfactant era. The four variables that were found to be most predictive for survival on logistic regression were systolic blood pressure at 6 h (odds ratio [OR], 1.3; 95% confidence interval [CI]: 1.11–1.44 1 mmHg), ventilatory index < 0.047 (OR, 4.8; 95%CI: 1.07–21.65), initial hemoglobin value (OR, 1.6; 95%CI: 1.09–2.34/1 g/dL), and base excess at 6 h (OR, 2.1; 95%CI: 1.08–1.84/5 mEq/L). Conclusions: A total of 53.2% of infants delivered between 23 and 24 weeks of gestation survived at discharge after introduction of surfactant replacement therapy. Early cardiopulmonary adaptation and initial hemoglobin value are key factors for survival in infants born at 23–24 weeks of gestation.     

Elevated iron status and risk of gestational diabetes mellitus: A systematic review and meta‐analysis

The aim of this systematic review and meta‐analysis of observational studies was to assess the relationship between elevated iron status, measured as hemoglobin and ferritin levels, and the risk of gestational diabetes mellitus (GDM). The present study was recorded in PROSPERO (2013:CRD42013005717). The selected studies were identified through a systematic review of scientific literature published in The Cochrane Library and PubMed/MEDLINE databases from their inception until March 10, 2016, in addition to citation tracking and hand‐searches. The search strategy of original articles combined several terms for hemoglobin, ferritin, pregnancy, and GDM. OR and 95% CI of the selected studies were used to identify associations between hemoglobin and/or ferritin levels with the risk of GDM. Summary estimates were calculated by combining inverse‐variance using fixed‐effects model. 2468 abstracts were initially found during the search. Of these, 11 with hemoglobin and/or ferritin data were selected for the meta‐analyses. We observed that high hemoglobin (OR = 1.52; 95% CI: 1.23–1.88), as well as ferritin (OR = 2.09; 95% CI: 1.48–2.96) levels were linked to an increased risk of GDM. Low heterogeneity was observed in hemoglobin (I² = 33.3%, P = 0.151) and ferritin (I² = 0.7%, P = 0.418) meta‐analyses, respectively. Publication bias was not appreciated. High hemoglobin or ferritin levels increase the risk of GDM by more than 50% and more than double, respectively, in the first and third trimester. Therefore, determining of hemoglobin or ferritin concentration in early pregnancy might be a useful tool for recognizing pregnant women at risk of GDM.     

β-Thalassemia with the IVS-l-1 (G → T) mutation in a Japanese girl

We analyzed the hemoglobins of a Japanese girl with β-thalassemia and those of her immediate family. DNA sequencing of the cloned β-globin gene from this patient revealed a point mutation at the IVS-I position 1 (G → T). This rare point mutation has been found in Asian Indians, but this is the first reported Japanese case.     

β–HCG Elevation in Wilms Tumor: An Uncommon Presentation

Wilms tumor (nephroblastoma) is a readily diagnosed common abdominal tumor in children. Rarely, it may present with factors that may confound the diagnosis. We report a 6‐year‐old female child who presented with a rapidly growing and invasive abdominal mass with the histopathologic features of Wilms tumor associated with an elevated serum beta human chorionic gonadotropin, which has not been previously reported in this condition.     

Hemoglobin A1c and fructosamine correlate in a patient with sickle cell disease and diabetes on chronic transfusion therapy

In patients with sickle cell disease (SCD) and diabetes mellitus (DM), hemoglobin A_1c (HbA_1c) is unreliable and the American Diabetes Association recommends monitoring long‐term glycemia by measuring serum glucose, but use of serum fructosamine (SF), a measurement independent of red cell lifespan, has been reported. SF as a screen for DM in SCD, however, is not standardized and its relationship to serum glucose has not been validated. Further, screening for DM was not adequately addressed in the 2014 National Heart, Lung, and Blood Institute (NHLBI) guidelines for SCD management. Blood transfusions, an important treatment for some patients with SCD, can also impact HbA_1c. We present a case of a patient with SCD and cystic fibrosis‐related diabetes on monthly chronic transfusions therapy (CTT) who had well‐correlated “steady state” HbA_1c and SF levels over time, suggesting for the first time these markers may actually be useful when following long‐term glycemic control in patients with SCD on CTT programs.     

Hb Adana (HBA2 or HBA1: c.179G > A) and alpha thalassemia: Genotype–phenotype correlation

Alpha thalassemia due to nondeletional mutations usually leads to more severe disease than that caused by deletional mutations. Devastating outcomes such as hydrops fetalis can occur with two nondeletional mutations, therefore warranting DNA‐based workup for suspected carriers with subtle hematological abnormalities for family counseling purposes. We describe three cases with hemoglobin (Hb) Adana, a nondeletional alpha chain mutation, compounded with an alpha globin gene deletion resulting in thalassemia intermedia. We review the literature, draw genotype–phenotype correlations from published cases of Hb Adana, and propose that this correlation can be used by clinicians to help direct diagnostic studies and urge hematologists to thoroughly workup high‐risk patients.     

Profound clinical and radiological response to BRAF inhibition in a 2‐month‐old diencephalic child with hypothalamic/chiasmatic glioma

Infants with low‐grade glioma (LGG) have a poor survival. BRAFV600E mutation has been identified in pediatric LGG; however, the use of BRAF inhibitors in infants has never been reported. A 2‐month‐old with V600E mutant hypothalamic/chiasmatic glioma progressed on chemotherapy resulting in profound visual loss, massive ascites, and diencephalic syndrome. Initiation of dabrafenib resulted in rapid and sustained disappearance of clinical symptoms and a profound sustained cytoreduction. BRAF inhibition was safely tolerated with dramatic clinicoradiological response, suggesting early targeted therapy is a viable option in infants with LGG. A re‐evaluation of current management paradigms in this population is warranted to leverage the potential benefit of upfront‐targeted therapies.     

The challenge of defining “ultra‐high‐risk” neuroblastoma

Given the biological and clinical heterogeneity of neuroblastoma, risk stratification is vital to determining appropriate treatment. Historically, most patients with high‐risk neuroblastoma (HR‐NBL) have been treated uniformly without further stratification. Attempts have been made to identify factors that can be used to risk stratify these patients and to characterize an “ultra‐high‐risk” (UHR) subpopulation with particularly poor outcome. However, among published data, there is a lack of consensus in the definition of the UHR population and heterogeneity in the endpoints and statistical methods used. This review summarizes our current understanding of stratification of HR‐NBL and discusses the complex issues in defining UHR neuroblastoma.     

CD56‐negative extranodal nasal type NK/T‐cell lymphoma

Extranodal natural killer (NK)/T‐cell lymphoma, nasal type, is a rare lymphoma that occurs predominantly in Asian adults. In this report, we describe the clinical and pathologic features of an unusual aggressive lymphoid neoplasm in a child and review the literature on NK/T‐cell lymphoma in children. The patient was a 4‐year‐old Native American male with facial swelling, lymphadenopathy, and fevers. Biopsy demonstrated neoplastic lymphoid cells that expressed CD3, CD8, TIA‐1, and EBV‐encoded RNA without CD56. The patient failed multiagent chemotherapy and died of therapy‐related complications. This case represents an extranodal NK/T‐cell lymphoma, nasal type, with an unusual lack of CD56. Pediatr Blood Cancer 2010;55:186–189. © 2010 Wiley‐Liss, Inc.     

Chemotherapy and interferon‐α treatment of Erdheim–chester disease

Erdheim–Chester disease (ECD) is a rare non‐Langerhans cell histiocytosis of an unknown origin. The prognosis of ECD is variable, and it mainly depends on the involved anatomic sites. The treatment modalities have not been standardized. Interferon‐α (IFN) has been reported to be effective in the management of ECD. We report here on an uncommon case with ECD in a 17‐year‐old female who had multiple lesions in the whole body and she was treated with chemotherapy and IFN. She has remained disease‐free for 2 years after the completion of treatment. Pediatr Blood Cancer. 2010;55:745–747. © 2010 Wiley‐Liss, Inc.     

Persistent jaundice in an infant with homozygous beta thalassemia due to co‐inherited Crigler–Najjar syndrome

Clinically apparent jaundice is unusual in patients with β‐thalassemia major. Co‐inheritance of Gilbert syndrome has been reported to cause hyperbilirubinemia in these subjects. Crigler–Najjar syndrome is another rare disorder of bilirubin metabolism caused by mutation in the gene coding the enzyme UGT1A1. We report a patient of β‐thalassemia major who presented with persistent jaundice due to co‐inherited Crigler–Najjar syndrome type 2 secondary to a novel mutation in UGT1A1 gene [homozygous base substitution at position 362 (GGT>AGT) in exon 3]. Pediatr Blood Cancer 2010;54:627–628. © 2009 Wiley‐Liss, Inc.