Recognition of a novel variant of phosphoglycerate kinase 1 deficiency PGK1 Galveston (c.472G > C) in a child with hemolytic anemia, neurologic dysfunction and myopathy.

The enzyme phosphoglycerate kinase 1 (PGK1) catalyzes the first ATP producing reaction in the glycolysis pathway. Certain mutations to the coding gene of PGK1 present clinically with varying manifestations including hemolytic anemia, central nervous system (CNS) dysfunction and myopathy. Various PGK1 mutations have been described in the literature at the clinical and molecular level. Herein, we describe a novel case PGK1 mutation (PGK1 Galveston) in a 4-year-old boy who presented with all three manifestations. We discuss the characteristic hematopathology findings from this patient as well as provide a comparison with previously described neuroimaging findings. The variable clinical presentation of this condition along with its inherent uniqueness provide a diagnostic challenge for physicians. This presentation will add to the current body of knowledge for this condition and help guide future investigation and management.

Evaluating the frequency of English language requirements in clinical trial eligibility criteria: A systematic analysis using ClinicalTrials.gov.

BACKGROUND: A number of prior studies have demonstrated that research participants with limited English proficiency in the United States are routinely excluded from clinical trial participation. Systematic exclusion through study eligibility criteria that require trial participants to be able to speak, read, and/or understand English affects access to clinical trials and scientific generalizability. We sought to establish the frequency with which English language proficiency is required and, conversely, when non-English languages are affirmatively accommodated in US interventional clinical trials for adult populations. METHODS AND FINDINGS: We used the advanced search function on ClinicalTrials.gov specifying interventional studies for adults with at least 1 site in the US. In addition, we used these search criteria to find studies with an available posted protocol. A computer program was written to search for evidence of English or Spanish language requirements, or the posted protocol, when available, was manually read for these language requirements. Of the 14,367 clinical trials registered on ClinicalTrials.gov between 1 January 2019 and 1 December 2020 that met baseline search criteria, 18.98% (95% CI 18.34%-19.62%; n = 2,727) required the ability to read, speak, and/or understand English, and 2.71% (95% CI 2.45%-2.98%; n = 390) specifically mentioned accommodation of translation to another language. The remaining trials in this analysis and the following sub-analyses did not mention English language requirements or accommodation of languages other than English. Of 2,585 federally funded clinical trials, 28.86% (95% CI 27.11%-30.61%; n = 746) required English language proficiency and 4.68% (95% CI 3.87%-5.50%; n = 121) specified accommodation of other languages; of the 5,286 industry-funded trials, 5.30% (95% CI 4.69%-5.90%; n = 280) required English and 0.49% (95% CI 0.30%-0.69%; n = 26) accommodated other languages. Trials related to infectious disease were less likely to specify an English requirement than all registered trials (10.07% versus 18.98%; relative risk [RR] = 0.53; 95% CI 0.44-0.64; p < 0.001). Trials related to COVID-19 were also less likely to specify an English requirement than all registered trials (8.18% versus 18.98%; RR = 0.43; 95% CI 0.33-0.56; p < 0.001). Trials with a posted protocol (n = 366) were more likely than all registered clinical trials to specify an English requirement (36.89% versus 18.98%; RR = 1.94, 95% CI 1.69-2.23; p < 0.001). A separate analysis of studies with posted protocols in 4 therapeutic areas (depression, diabetes, breast cancer, and prostate cancer) demonstrated that clinical trials related to depression were the most likely to require English (52.24%; 95% CI 40.28%-64.20%). One limitation of this study is that the computer program only searched for the terms "English" and "Spanish" and may have missed evidence of other language accommodations. Another limitation is that we did not differentiate between requirements to read English, speak English, understand English, and be a native English speaker; we grouped these requirements together in the category of English language requirements. CONCLUSIONS: A meaningful percentage of US interventional clinical trials for adults exclude individuals who cannot read, speak, and/or understand English, or are not native English speakers. To advance more inclusive and generalizable research, funders, sponsors, institutions, investigators, institutional review boards, and others should prioritize translating study materials and eliminate language requirements unless justified either scientifically or ethically.

Steroid-responsive atypical marginal zone hyperplasia of the lip in a child.

Atypical marginal zone hyperplasia (AMZH) is a recently described disease entity seen mainly in children. AMZH most commonly affects tonsils and appendices. Cutaneous AMZH is rare. The authors report here a recurrent AMZH in the lip of a 9-year-old child who presented originally with a lip swelling for approximately 3 months. The lip lesion recurred after each incomplete excision for 4 times. Pathologically, the lesion demonstrated marginal zone B-cell hyperplasia with kappa monoclonality by flow cytometry and immunohistochemistry studies. Lymphoepithelial lesions were noted with involvement of minor salivary glands. Polymerase chain reaction for immunoglobulin heavy-chain gene rearrangement has been repeatedly negative. Polymerase chain reaction for Borrelia species DNA was negative on both paraffin-embedded tissue and plasma. Serum antibodies IgG and IgM for Helicobacter Pylori were positive. A diagnosis of AMZH was made. Two courses of anti H. Pylori therapy did not improve the lip lesion, which completely regressed after a course of prednisone therapy. With differential diagnosis of cutaneous marginal zone lymphoma, the case illustrated diagnostic challenges, especially with recurrent lesions. This is the first case of recurrent cutaneous AMZH that has uncharacteristic kappa light-chain restriction. AMZH should be considered in children with mucocutaneous lesions with features of marginal zone lymphoma.

Dyserythropoiesis in a child with pyruvate kinase deficiency and coexistent unilateral multicystic dysplastic kidney.

Pyruvate kinase (PK) deficiency is the commonest enzyme deficiency in the glycolytic pathway leading to hemolytic anemia secondary to decreased Adenosine Triphosphate (ATP) synthesis in the red cells. synthesis. PK deficiency due to mutations in the PKLR (1q21) gene leads to highly variable clinical presentation ranging from severe fetal anemia to well compensated anemia in adults. We describe dyserythropoiesis in the bone marrow of a child with transfusion dependent anemia and unilateral multicystic dysplastic kidney (MCDK) mimicking Congenital Dyserythropoietic Anemia type I (CDA type I). Persistently low erythrocyte PK levels and double heterozygous mutations present in the PKLR gene confirmed the diagnosis of PK deficiency.

Severe Thrombocytosis in a Newborn with Subcutaneous Fat Necrosis and Maternal Chorioamnionitis.

BACKGROUND: Subcutaneous fat necrosis (SFN) is a form of transient panniculitis that presents commonly in infants with a history of perinatal insult, particularly hypothermia. It is characterized by subcutaneous nodules and plaques that appear over bony prominences on cheeks, shoulders, buttock, and thighs. SFN is usually associated with various complications including hypercalcemia, thrombocytopenia, hypertriglyceridemia, and hyperglycemia. Case Presentation. We present a unique case of a female infant with a history of maternal chorioamnionitis who presented with SFN at 11 days of life with thrombocytosis. The platelet count decreased during the hospital stay, and thrombocytosis resolved over the course of the next two weeks. She did not have any other hematological or metabolic abnormalities associated with SFN. CONCLUSION: Infants with perinatal stress are at increased risk of developing SFN during the first month of life. Infants with a diagnosis of SFN should be monitored closely for various hematological and metabolic abnormalities that can have serious consequences.

Incidental finding of a huge ovarian serous cystadenoma in an adolescent female with menorrhagia.

Pelvic tumors in adolescent females are very uncommon. While the most common presentation is pelvic discomfort, we report the case of a 14-year-old female presenting with menorrhagia which is an unusual initial complaint for a large pelvic tumor. Adolescent females who present with heavy menstrual bleeding initially undergo assessment to rule out a bleeding disorder. In this case, careful history and physical examination helped in making a quick diagnosis and management. Ultrasound of abdomen showed a huge cystic mass due to serous cystadenoma of the ovary.

Sporadic Burkitt Lymphoma Presenting as Acute Pancreatitis, Concurrent Sinusitis, and Enlarged Adenoids.

Pancreatitis and sinusitis as presentations of Burkitt lymphoma are uncommon and rarely described in children. We describe here the case of a child who presented with symptoms suggestive of sinusitis unresponsive to antibiotics, with subsequent development of abdominal symptoms due to pancreatitis. He was eventually diagnosed with Burkitt lymphoma.