Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8–13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05–6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50–75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life. Funding Pfizer, Amgen, Merck Sharp & Dohme, Sanofi–Aventis, Daiichi Sankyo, and Regeneron

Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Corrigendum to “Vitamin D status in children with epilepsy treated with levetiracetam monotherapy” (Epilepsy Research (2018) 148 (116), (S0920121118304431) (10.1016/j.eplepsyres.2018.09.003))

The authors regret that one author (A. Prasouli) was not included in the authors list. The correct authors list and their affiliations are: Achilleas Attilakos MD a , Maria Tsirouda RN a , Argiris Dinopoulos MD a , Alexia Prasouli MD b , Anastasia Garoufi MD c a Third Department of Pediatrics, National and Kapodistrian University of Athens, “Attikon” Hospital, Athens, Greece b Department of Social and Developmental Pediatrics, Institute of Child Health, Athens, Greece c Second Department of Pediatrics, National and Kapodistrian University of Athens, “Panagiotis and Aglaia Kyriakou” Children's Hospital Athens, Greece The authors would like to apologize for any inconvenience caused. © 2018 Elsevier B.V

Hypercalciuria in children with febrile convulsions

Background: The purpose of the present study was to investigate whether idiopathic hypercalciuria may be implicated in the pathogenesis of febrile convulsions. Methods: We studied 38 children (22 boys) with febrile convulsions (mean (+/-SD) age 3.25+/-1.09 years) and 45 healthy children (28 boys) of similar age who served as controls. Twenty-four hour urine calcium and phosphate, as well as serum calcium, phosphate, alkaline phosphatase and intact parathyroid hormone (PTH) concentrations were determined. Results: Hypercalciuria (urine Ca >4.0 mg/kg bodyweight per 24 h) was found in nine children with febrile convulsions (23.7%) and in three controls (6.7%). Hypercalciuric children excreted significantly more phosphate in their urine (37.0+/-11.6 mg/kg bodyweight per 24 h) than normocalciuric children (18.7+/-8.7 mg/kg bodyweight per 24 h) and controls (20.2+/-7.6 mg/kg bodyweight per 24 h). They also had higher serum intact PTH concentrations (49.87+/-15.36 pg/mL) than normocalciuric (35.39+/-15.67 pg/mL) and control children (28.21+/-14.00 pg/mL). According to the calcium-loading test, eight of nine children with hypercalciuria had the renal type of the disorder. Furthermore, hypercalciuric children had significantly more convulsive episodes (2.77+/-1.98) than normocalciuric children (1.86+/-1.24). Conclusions: Our results suggest that renal hypercalciuria may be implicated in the pathogenesis of febrile convulsions

Acute renal failure in a child with thrombocytopenic purpura caused by acute epstein-barr virus infection after treatment with anti-D immunoglobulin

Immune thrombocytopenia (ITP) in children is usually a benign, self-limiting disorder. An acute Epstein-Barr virus (EBV) infection usually causes atypical lymphocytosis and mild decrease in platelets. Severe thrombocytopenia is an extremely rare complication. Anti-D immunoglobulin has been used for treatment of ITP in Rh(D)-positive nonsplenectomized patients. Severe hemolysis and acute renal failure are extremely rare complications that may be aggravated by the presence of an acute EBV infection. It is believed that anti-D immunoglobulin triggers an unusual virus-induced immune response causing hemolysis. We present a 4-year-old girl with ITP caused by an acute EBV infection that developed acute kidney injury following treatment with anti-D immunoglobulin. The patient recovered completely from thrombocytopenia and renal dysfunction. Intravascular hemolysis and acute kidney injury are consistent with anti-D immunoglobulin mechanism of action. Pediatric patients treated with anti-D immunoglobulin for ITP should be closely monitored for signs and symptoms of hemolysis that may be aggravated by the presence of EBV infection leading to impaired renal function. Copyright © 2013 Lippincott Williams & Wilkins

Advancements in sex estimation using the diaphyseal cross-sectional geometric properties of the lower and upper limbs

This paper introduces an automated method for estimating sex from the lower and upper limbs based on diaphyseal CSG properties. The proposed method was developed and evaluated using 389 femurs, 412 tibias, and 404 humeri of adult individuals from a modern Greek reference sample, the Athens Collection. The skeletal properties, which were extracted with the CSG-Toolkit, were analyzed with step-wise DFA (evaluated with LOOCV) and subsequently with RBF kernel SVM supervised learning. SVM cross-validation was based on a 20-fold stratified random sample splitting as well as a chronological split based on year of birth to further assess the effect of secular change in sex estimation capacity. Maximum cross-validated classification accuracy from step-wise DFA reached 94.8% for the femur, 94.7% for the tibia, and 97.3% for the humerus, whereas SVM cross-validated results were similar although slightly lower, mainly due to the more strict cross-validation scheme. Our results suggest that the proposed sex estimation method is reasonably robust to secular change, since there was limited loss in classification accuracy between different chronological groups, despite the presence of secular change in stature of the Greek population during the examined period. The proposed method has been implemented as a function for the GNU Octave environment, named estimate_sex, which comprises a self-intuitive graphical user interface for facilitating sex estimation and is freely available under a suitable license. © 2020, Springer-Verlag GmbH Germany, part of Springer Nature

The potential of novel peptides in the management of children with Congenital Heart Disease: Above and beyond the BNP

Congenital Heart Disease (CHD) constitutes a common cause of major congenital abnormalities with prevalence around 8.2 per 1000 live births in Europe. Despite the important advances in the diagnosis, treatment and management of CHD patients throughout the years, it remains a challenge how to better manage the children with CHD using the biomarkers. However, in the last decade, B-type Natriuretic Peptide (BNP) and less often Adrenomedullin (ADM) and Urotensin II (UT II) have become the focus of research, in view of the improvement in the management of patients with CHD. Moreover, despite crescent evidences supporting the use of BNP as diagnostic and prognostic marker in children with CHD, its use remains limited and guidelines/expert consensus recommendations are lacking. Adrenomedullin (ADM) and Urotensin II (UT II) are two potent vasoactive peptides that might play a role in the development of pulmonary hypertension. Future studies are needed to explore the role of both peptides as biomarkers of pulmonary hypertension and their prognostic significance on the development of pulmonary hypertension in CHD patients. © 2016 Elsevier Ireland Lt

Too short stature, too many stigmata

Dyskeratosis congenita (DC) is a rare disease characterised by bone marrow failure and skin manifestations. Patients with DC may exhibit short stature that is not usually related to growth hormone (GH) deficiency. Replacement treatment with GH should be done cautiously as it can predispose to haematological malignancy. We present a 10-year-old boy with DC and GH deficiency