Pyruvate kinase deficiency (PKD) is the most common enzyme defect of glycolysis and an important cause of hereditary, nonspherocytic hemolytic anemia. The disease has a worldwide geographical distribution but there are no verified data regarding its frequency. Difficulties in the diagnostic workflow and interpretation of PK enzyme assay likely play a role. By the creation of a global PKD International Working Group in 2016, involving 24 experts from 20 Centers of Expertise we studied the current gaps in the diagnosis of PKD in order to establish diagnostic guidelines. By means of a detailed survey and subsequent discussions, multiple aspects of the diagnosis of PKD were evaluated and discussed by members of Expert Centers from Europe, USA, and Asia directly involved in diagnosis. Broad consensus was reached among the Centers on many clinical and technical aspects of the diagnosis of PKD. The results of this study are here presented as recommendations for the diagnosis of PKD and used to prepare a diagnostic algorithm. This information might be helpful for other Centers to deliver timely and appropriate diagnosis and to increase awareness in PKD.

Anemia is a global health problem in all age groups. According to World Health Organization (WHO), approximately 40% of pregnant women are anemic. Iron deficiency anemia (IDA) due to nutritional deficiency is the most common cause. The incidence of IDA varies worldwide depending on the socioeconomic status, but it remains the leading cause even in developed countries. Physiologic anemia of pregnancy due to relatively higher expansion of blood volume in comparison with elevated red blood cell mass also occurs frequently. Complete blood count (CBC) in the first trimester is recommended for all pregnant women to screen for anemia. The screening of pregnant women for IDA in absence of anemia is still debatable. If IDA is suspected, ferritin level of <30 ng/ml is diagnostic. Iron supplementation is recommended for all pregnant women to compensate the increased demand.

Background: Acute bilirubin encephalopathy (ABE) is a potentially devastating condition that can lead to death or life-long neurodevelopmental handicaps. ABE is particularly tragic because it is, in theory, completely preventable. Progress toward its prevention has been hampered by the perception that the extreme hyperbilirubinemia giving rise to ABE typically has no clear causation, with the majority of previous cases being labeled as “idiopathic” neonatal jaundice. Objectives: This research briefing is intended to inform readers of a new prospective study aimed at clarifying the causes of ABE. This is accomplished by identifying qualifying patients with ABE anywhere in the USA and then documenting their clinical characteristics and the results of testing 28 specific genetic associations in a web-based, institutional review board-approved, REDCap (research electronic data capture) deidentified registry. Methods: In this research briefing, we present an overview of ABE and discuss the problem that most patients in the past have been labeled as having “idiopathic” hyperbilirubinemia. We also present data supporting a new theory that most (perhaps all) ABE patients have mutations or polymorphisms in genes involved in bilirubin production or metabolism. We introduce a new registry seeking to enroll 100 neonates with ABE as a voluntary, deidentified database, with next generation sequencing of 28 genes involved in bilirubin production/metabolism provided to enrollees at no cost. Results and Conclusions: The Neonatal Acute Bilirubin Encephalopathy Registry (NABER) study will correlate deidentified clinical and genetic data in order to clarify the underlying causes of hyperbilirubinemia in current ABE patients. We maintain that the improved understanding this study produces will constitute a needed step toward devising new clinical pathways and strategies for preventing ABE in neonates.

Three children between the ages of 18 months and four years presented with a discharging sinus or sinuses at the wrist due to a ‘sacred’ thread (the Moli Dhaga) which had been tied around it. This thread had been forgotten by the parents and had become embedded in the soft tissues of the wrist. Plain radiographs showed a circumferential constriction in the soft tissue shadow in all three. In two, there was a periosteal reaction in the distal radius or ulna with an indentation which we have called the constriction sign. Surgical removal of the buried thread was successful in all cases.

We evaluated a neonate with severe jaundice but a negative family history. Spherocytes were present and suspected hereditary spherocytosis was confirmed by osmotic fragility and eosin-5-maleimide erythrocyte staining. We found he was a compound heterozygote for two pathogenic mutations in the gene encoding α-spectrin: a previously reported αLEPRA inherited from his asymptomatic mother, and a novel α-spectrin mutation in intron 45 +1 disrupting the consensus splice site, from his asymptomatic father.