Managing Undernutrition in Pediatric Oncology: A Consensus Statement Developed Using the Delphi Method by the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology.

"Managing Undernutrition in Pediatric Oncology" is a collaborative consensus statement of the Polish Society for Clinical Nutrition of Children and the Polish Society of Pediatric Oncology and Hematology. The early identification and accurate management of malnutrition in children receiving anticancer treatment are crucial components to integrate into comprehensive medical care. Given the scarcity of high-quality literature on this topic, a consensus statement process was chosen over other approaches, such as guidelines, to provide comprehensive recommendations. Nevertheless, an extensive literature review using the PubMed database was conducted. The following terms, namely pediatric, childhood, cancer, pediatric oncology, malnutrition, undernutrition, refeeding syndrome, nutritional support, and nutrition, were used. The consensus was reached through the Delphi method. Comprehensive recommendations aim to identify malnutrition early in children with cancer and optimize nutritional interventions in this group. The statement underscores the importance of baseline and ongoing assessments of nutritional status and the identification of the risk factors for malnutrition development, and it presents tools that can be used to achieve these goals. This consensus statement establishes a standardized approach to nutritional support, aiming to optimize outcomes in pediatric cancer patients.

Evaluation of Arsenic and Cobalt Levels in Pediatric Patients Receiving Long-Term Parenteral Nutrition.

This study continues the research in which we determined the concentration of aluminum in children receiving long-term parenteral nutrition (LPN). Since our results were interesting, we decided to assay arsenic (As) and cobalt (Co) in the collected material, which, like aluminum, constitute contamination in the mixtures used in parenteral nutrition. Excesses of these trace elements in the human body are highly toxic, and deficiencies, particularly in the case of Co, can lead to various complications. The aim of this study was to determine the impact of LPN in children on their serum levels of As and Co, as well as the excretion of these elements in urine, and to compare them with a control group of healthy children. The study group consisted of 83 children receiving home parenteral nutrition from two Polish centers, while the control group included 121 healthy children. In both groups, the levels of As and Co in serum and urine were measured. The elemental compositions of the samples were determined using inductively coupled plasma mass spectrometry (ICP-MS). It was demonstrated that the children receiving LPN did not have increased As exposure compared to the controls. Greater exposure compared to the control group was shown for Co. In conclusion, children receiving LPN are not exposed to As, and even though the concentrations of Co in serum and urine were higher in the LPN group than in the healthy controls, neither trace element poses a health threat to children requiring LPN.

Neutrophil functions in patients with neutropenia due to glycogen storage disease type 1b treated with empagliflozin.

ABSTRACT: Neutropenia and neutrophil dysfunction in glycogen storage disease type 1b (GSD1b) are caused by the accumulation of 1,5-anhydroglucitol-6-phosphate in granulocytes. The antidiabetic drug empagliflozin reduces the concentration of 1,5-anhydroglucitol (1,5-AG), thus restoring neutrophil counts and functions, leading to promising results in previous case reports. Here, we present a comprehensive analysis of neutrophil function in 7 patients with GSD1b and 11 healthy donors, aiming to evaluate the immediate (after 3 months) and long-term (after 12 months) efficacy of empagliflozin compared with the reference treatment with granulocyte-colony stimulating factor (G-CSF). We found that most patients receiving G-CSF remained neutropenic with dysfunctional granulocytes, whereas treatment with empagliflozin increased neutrophil counts and improved functionality by inhibiting apoptosis, restoring phagocytosis and the chemotactic response, normalizing the oxidative burst, and stabilizing cellular and plasma levels of defensins and lactotransferrin. These improvements correlated with the decrease in serum 1,5-AG levels. However, neither G-CSF nor empagliflozin overcame deficiencies in the production of cathelicidin/LL-37 and neutrophil extracellular traps. Given the general improvement promoted by empagliflozin treatment, patients were less susceptible to severe infections. G-CSF injections were therefore discontinued in 6 patients (and the dose was reduced in the seventh) without adverse effects. Our systematic analysis, the most extensive reported thus far, has demonstrated the superior efficacy of empagliflozin compared with G-CSF, restoring the neutrophil population and normal immune functions. This trial was registered as EudraCT 2021-000580-78.

Unexpected Serum and Urine Aluminum Concentrations in Pediatric Patients on Home Parenteral Nutrition.

The intravenous supply of aluminum (Al) present in parenteral nutrition solutions poses a high risk of the absorption of this element, which can result in metabolic bone disease, anemia, and neurological complications. The aim of this study is to determine the impact of long-term parenteral nutrition (PN) in children on serum Al concentration and its urinary excretion compared to healthy children. We evaluated serum Al concentrations and its urinary excretion in patients enrolled in the Polish home parenteral nutrition (HPN) program between 2004 and 2022. The study group included 83 patients and the control group consisted of 121 healthy children. In children whose PN was started in the neonatal period, we found higher serum Al concentrations and higher urinary Al excretion than in other subjects whose PN was started later. Only 12% of the children on chronic parenteral nutrition had serum Al concentrations of less than 5 µg/L. Healthy children in the control group had higher serum Al concentrations than those in the parenteral nutrition group, which may indicate the influence of one's environment and diet on Al serum levels.

S100B Protein but Not 3-Nitrotyrosine Positively Correlates with Plasma Ammonia in Patients with Inherited Hyperammonemias: A New Promising Diagnostic Tool?

Individuals with inherited hyperammonemias often present developmental and intellectual deficiencies which are likely to be exaggerated by hyperammonemia episodes in long-term outcomes. In order to find a new, systemic marker common to the course of congenital hyperammonemias, we decided to measure the plasma level of S100 calcium-binding protein B (S100B), which is associated with cerebral impairment. Further, we analyzed three mechanistically diverged but linked with oxidative-nitrosative stress biochemical parameters: 3-nitrotyrosine (3-NT), a measure of plasma proteins' nitration; advanced oxidation protein products (AOPP), a measure of protein oxidation; and glutathione peroxidase (GPx) activity, a measure of anti-oxidative enzymatic capacity. The plasma biomarkers listed above were determined for the first time in congenital hyperammonemia. Also, the level of pro- and anti-inflammatory mediators (i.e., IL-12, IL-6, IL-8, TNF-α, IL-1ß, and IL-10) and chemokines (IP-10, MCP-1, MIG, and RANTES) were quantified. S100B was positively correlated with plasma ammonia level, while noticeable levels of circulating 3-NT in some of the patients' plasma did not correlate with ammonia concentration. Overall, the linear correlation between ammonia and S100B but not standard oxidative stress-related markers offers a unique perspective for the future identification and monitoring of neurological deficits risk-linked with hyperammonemia episodes in patients with inherited hyperammonemias. The S100B measure may support the development of therapeutic targets and clinical monitoring in these disorders.

Immune Response to SARS-CoV-2 Infections in Children with Secondary Immunodeficiencies.

BACKGROUND AND PURPOSE: It is a matter of research, whether children with immunodeficiencies are able to generate an effective immune response to prevent SARS-CoV-2 reinfection. This study aimed to evaluate and compare the seroconversion rates and changes of lymphocyte subsets during COVID-19 in immunocompetent children and those with secondary immunodeficiencies. METHODS: In 55 children - 28 immunocompromised and 27 immunocompetent - hospitalized with confirmed SARS-CoV-2 infection, the level of IgG antibodies against the Spike protein was determined on two to three occasions. In those children from the study group whose immunosuppressive treatment did not alter during the study (n = 13) and in selected children from the control group (n = 11), flow cytometric evaluation of lymphocyte subsets was performed twice - 2 weeks and 3 months post-infection. RESULTS: Seroconversion reached 96.3% in both studied groups; however, the immunocompromised cohort achieved lower titers of detectable anti-S antibodies. There was no correlation between seroconversion or titers of antibodies and the total number of lymphocytes or their subsets. In the immunocompetent cohort, we reported a significant decrease in NK cells during the infection. In this group and the entire study population, a positive correlation was noticed between the CD4 + /CD8 + T cell ratio and the severity of COVID-19 pneumonia. CONCLUSIONS: Children with secondary immunodeficiencies seroconvert in equal percentages but with a significantly lower titer of anti-S antibodies compared to their immunocompetent peers. The lower number of NK cells in the immunocompetent cohort may result from their participation in antiviral immunity, whereas reduced CD4 + /CD8 + T cell ratios among immunocompromised children may be a protective factor against a severe COVID-19.

Long-COVID in immunocompromised children.

Coronavirus disease 2019 (COVID-19) can lead to an illness characterized by persistent symptoms which affect various organs and systems, known as long-COVID. This study aimed to assess the prevalence and clinical characteristics of long-COVID in children with immunodeficiency, in comparison to those without. A self-constructed questionnaire was created, which included questions regarding the child's general health, the course of their COVID-19, their symptoms of long-COVID and its impact on their daily functioning, the diagnosis of multisystem inflammatory syndrome (MIS-C), and vaccination status. The questionnaire was completed by parents of 147 children - 70 children with a diagnosis of immunodeficiency (47.6%) and 77 who were immunocompetent (52.4%). Immunocompetent children were more significantly affected by long-COVID than those immunocompromised. Its prevalence in the first 12-week post-infection was 60.0% and 35.7% in these groups, respectively. Beyond this period, these percentages had dropped to 34.6% and 11.43%, respectively. Children who were immunocompetent reported more often symptoms of fatigue, reduced exercise tolerance, and difficulty concentrating. Meanwhile, there was a slight increase in complaints of gastrointestinal symptoms in immunocompromised patients. The risk of developing long-COVID increased with age and COVID-19 severity in both groups. Furthermore, the daily activities of immunocompetent children were limited more frequently (41.8%) than for those who were immunocompromised (25%). CONCLUSIONS: Although immunocompromised children experienced long-COVID, its prevalence and impact on daily functioning were significantly lower than among immunocompetent children. However, as the pathomechanisms of long-COVID are not yet fully understood, it is not currently possible to fully explain these findings. WHAT IS KNOWN: • Long COVID is characterized by persistent symptoms following COVID-19, which can affect various tissues and organs, as well as mental health. • Due to the similar course of COVID-19 - mainly mild or asymptomatic - among children with and without immunodeficiency, the question arises, over whether the prevalence and severity of long-COVID is also similar in both groups. WHAT IS NEW: • Immunocompromised children also suffer from long-COVID, but the prevalence is significantly lower than in the immunocompetent group of children. • The potential causes of less frequent and milder long-COVID in this group may be the milder course of COVID-19 and the state of reduced immunity protecting against neuroinflammation.

BCG Moreau Polish Substrain Infections in Patients With Inborn Errors of Immunity: 40 Years of Experience in the Department of Immunology, Children's Memorial Health Institute, Warsaw.

Objective: We aimed to assess BCG (Bacillus Calmette-Guérin) complications in patients with Inborn Errors of Immunity (IEI), according to the inherited disorders and associated immunological defects, as well as the different BCG substrains. Material: We studied adverse reactions to the locally-produced BCG Moreau vaccine, analyzed in patients with IEI diagnosed between 1980 and 2020 in the Department of Immunology, Children's Memorial Health Institute (CMHI), Warsaw. These results were compared with previously published studies. Results: Significantly fewer disseminated BCG infections (BCGosis) were found in 11 of 72 (15%) SCID (Severe Combined Immunodeficiency) NK (Natural Killer)-phenotype patients, when compared with the 119 out of 349 (34%) (p = 0.0012) patients with SCID with BCG in other countries. Significantly fewer deaths caused by BCGosis were observed (p = 0.0402). A significantly higher number of hematopoietic stem cell transplantations (HSCTs) were performed in the CMHI study (p = 0.00001). BCGosis was found in six patients with Mendelian susceptibility to mycobacterial diseases (MSMD). Other patients with IEI prone to BCG complications, such as CGD (Chronic Granulomatous Disease), showed no case of BCGosis. Conclusion: The BCG Moreau substrain vaccine, produced in Poland since 1955, showed genetic differences with its parental Brazilian substrain together with a superior clinical safety profile in comparison with the other BCG substrains, with no BCGosis in patients with IEI other than SCID and MSMD. Our data also confirmed significantly fewer cases of BCGosis and deaths caused by BCG infection in patients with SCID with this vaccine substrain. Finally, they confirmed the protecting role of NK cells, probably via their production of IFN-γ.

Clinical characteristics and long-term outcomes of patients with glycogen storage disease type 1b: a retrospective multi-center experience in Poland.

Glycogen storage disease type 1b (GSD 1b) is an inherited metabolic defect caused by a deficiency of microsomal glucose-6-phosphate (G6P) transport protein across the endoplasmic reticulum membrane. Patients with GSD 1b have hypoglycemia episodes, lactate acidosis, hypertriglyceridemia, hypercholesterolemia, hyperuricemia, neutropenia and in imaging studies hepatomegaly and/or nephromegaly. The primary goals of treatment are to maintain proper blood glucose levels and to increase the number of properly functioning neutrophils. The aim of the study was a retrospective analysis of the clinical picture and treatment results of pediatric patients with type 1b glycogen storage disease from Poland. The study included 13 patients from 3 clinical centers, with a median age at diagnosis as 5 months. In 11/13 patients, the diagnosis was confirmed by molecular test, by the presence of pathogenic variants on both alleles of the SLC37A4 gene. Ten out of 13 patients developed the first symptoms in the form of severe infection (sepsis and/or pneumonia) already in the neonatal-infant period. A hypoglycemia episode was observed before diagnosis in 8/13 patients, of which 4/8 patients presented symptoms in the form of generalized relaxation and/or seizures. Two patients developed hypertension, and 4/13 required long-term treatment of inflammatory bowel disease.

Partial Hydrolyzed Protein as a Protein Source for Infant Feeding: Do or Don't?

Exclusive breastfeeding until the age of six months is the recommended feeding method for all infants. However, this is not possible for every infant. Therefore, a second choice of feeding, as close as possible to the gold standard, is needed. For historical reasons, this has been cow's-milk-based feeding. This paper discusses if this second-choice feeding method should contain intact protein or partially hydrolyzed proteins. The limited data available indicates that mother's milk is relatively rich in bioactive peptides. Whether partially hydrolyzed protein might be a protein source closer to human milk protein content than intact cow's milk needs further research. However, more research on protein and bioactive peptides in mother's milk should be a priority for future scientific development in this field. Results of such research will also provide an answer to the question of which option would be the best second choice for infant feeding if sufficient breast milk is not available.

Sodium-glucose cotransporter type 2 channel inhibitor: Breakthrough in the treatment of neutropenia in patients with glycogen storage disease type 1b?

Glycogen storage disease type 1b (GSD 1b) is an inherited metabolic defect caused by biallelic mutations in the SLC37A4 gene encoding microsomal glucose-6-phosphate (G6P) transporter in the endoplasmic reticulum (ER) membrane. Ineffective G6P transport into the ER leads to hypoglycaemia, hyperlactatemia, hyperuricemia, hypertriglyceridemia, hepato- and/or nephromegaly. Clinical manifestations of the disease include recurrent, severe infections and inflammatory bowel (Crohn-like) caused by neutropenia and diminished bactericidal and fungicidal activity of neutrophils. Granulocyte colony-stimulating factor (G-CSF) administration is currently a standard therapy to prevent adverse effects of neutropenia, but the treatment is associated with a high risk of severe side effects. On the other hand, short-treatment with sodium-glucose cotransporter type 2 inhibitor - empagliflozin (EMPA) was reported to act directly on the mechanism of neutropenia and neutrophil dysfunction in GSD 1b. We observed significant improvement in clinical and laboratory parameters after introducing EMPA to treatment, that is reduced frequency of infections, lower number of bowel movements, and improved postoperative wound healing. EMPA is effective in the treatment of neutropenia in our GSD 1b patients, which allows for dose reduction and even withdrawal of G-CSF. We did not observe any significant side effects of EMPA treatment in our patients.

Different Course of SARS-CoV-2 Infection in Two Adolescents With Other Immunosuppressive Factors.

Even after two years of the Coronavirus Disease 2019 (COVID-19) pandemic, despite known risk factors, we are still unable to predict the severity of the infection in specific patients. Due to the contradictory data, the protective role of immunosuppression in preventing the severe course of the infection remains uncertain. Therefore, we want to discuss the influence of several immunosuppressive factors on the COVID-19 pattern in children, based on two case reports regarding 17-year-old boys with other immunosuppressive factors and a completely different course of the disease. The first patient suffered from AIDS, syphilis and primary central nervous system B-cell lymphoma, treated with radiotherapy. He experienced a light path of the infection, presenting only periodically appearing cough with no X-ray inflammatory changes. Nevertheless, due to the risk of severe COVID-19 and transient hypoxia, remdesivir was administered. He remained in a generally good condition and his follow-up did not reveal any noticeable complications. The second patient was characterised by Down syndrome, obesity, polyarteritis nodosa and chronic immunosuppressive therapy. He developed massive pneumonia, required treatment in the intensive care unit with the use of mechanical ventilation, remdesivir and anakinra. Despite the initial improvement of his general condition, including the degree of lung involvement and respiratory function, he developed an intracerebral haemorrhage, leading to brain herniation and ultimately death. In conclusion, HIV infection, oncological and immunosuppressive treatment do not seem to predispose to the severe course of COVID-19, whereas Down syndrome and obesity do.

Clinical characteristics of Kawasaki disease in Polish children: A retrospective study.

BACKGROUND: Kawasaki disease (KD), an acute, generalized vasculitis, is associated with an increased risk of coronary heart disease and is the most common cause of acquired heart disease in childhood. The incidence of KD is increasing worldwide. AIMS: Our study aims to analyze KD's clinical course in children and to evaluate risk factors for persistent changes in coronary vessels after 6-8 weeks of treatment. METHODS: The retrospective analysis included patients with KD hospitalized in a single tertiary carehospital. The diagnosis, as well as treatment, were based on the current worldwide treatment standards. The clinical course, selected laboratory parameters, the treatment effect, and following cardiac complications were analyzed in different age groups. RESULTS: In the years 2006-2019, 140 patients aged from two months to 16 years: 52 girls and 88 boys, were diagnosed with KD. Coronary artery aneurysms (CAA) at weeks 6-8 of disease were found in 16% of patients. Boys and infants were more likely to develop aneurysms at weeks 6-8 of the disease (P = 0.045; P = 0.03; respectively). The CAA frequency was related to the atypical course (P = 0.02), late diagnosis (P = 0.04), presence of changes in the coronary arteries at the time of diag nosis (P<0.001), immunoglobulin resistance (P = 0.002), a lower hemoglobin concentraction (P<0.001), and a higher platelet count (P = 0.02). There were 28% of patients resistant to first-line time treatment. In this group, we found CAA in 31% of children. CONCLUSIONS: We found that late diagnosis, low hemoglobin level, high platelet count, CAA presence at diagnosis, atypical course of KD, and resistance to intravenous immunoglobulins are predictors of CAA after 6-8 weeks in KD patients.

Anti-inflammatory Treatment of Kawasaki Disease: Comparison of Current Guidelines and Perspectives.

Kawasaki disease (KD), an acute, generalized vasculitis, is associated with an increased risk of coronary heart disease and is the most common cause of acquired heart disease in childhood. The incidence of KD is increasing worldwide. There are numerous international treatment guidelines. Our study aims to perform the first one so far comparison of them. While the gold standard therapy remains still the same (intravenous immunoglobulins and aspirin), there is currently a lack of evidence for choosing optimal treatment for high-risk patients and refractory KD. In this review, we also discuss the treatment of complications of KD and Kawasaki-like phenotypes, present an anti-inflammatory treatment in the light of new scientific data, and present novel potential therapeutic targets for KD.

Prevalence and Course of SARS-CoV-2 Infection among Immunocompromised Children Hospitalised in the Tertiary Referral Hospital in Poland.

The aim of this retrospective study was the assessment of the prevalence, clinical characteristics, and the comparison of the course of SARS-CoV-2 infection in children with and without immunodeficiency that were admitted to the COVID-19 Subunit of the tertiary referral hospital in Warsaw, Poland. We analysed 313 children hospitalised in the COVID-19 Subunit. The analysis was performed on the total study group and subgroups of children with and without immunodeficiency. In each group, clinical data and laboratory test results were analysed. Of the 68 children with isolated fevers, only seven (11.76%) were diagnosed with COVID-19, whereas among those with the accompanying features of respiratory or gastrointestinal infection, only one (3.23%) and ten (16.95%) patients tested positive, respectively. In both groups, the course of the infection was mainly asymptomatic or mild. The children with immunodeficiencies had lower white blood cell and lymphocyte counts, lower haemoglobin levels, and higher urea levels but did not differ in other biochemical variables. To conclude, the most frequently reported symptoms of COVID-19 indicate that this disease among children is only a small percentage. In both groups, the responses to the infection were comparable in terms of the mild clinical symptoms and the laboratory test results. Therefore, SARS-CoV-2 infection should not alter the chronic treatment of underlying diseases.

Home Artificial Nutrition in Polish Children: An Analysis of 9-Year National Healthcare Provider Data.

BACKGROUND: Home artificial nutrition (HAN) is a developing method of treatment that reduces the need for hospitalizations. The epidemiology of pediatric HAN in Poland has not yet been covered in detail. This study is a longitudinal nationwide analysis of incidence, prevalence, and patients' profile for HAN in Polish children. METHODS: Assessment of National Health Fund (NFZ) data covering all pediatric patients treated with HAN in Poland between 2010 and 2018. RESULTS: HAN was received by 4426 children, 65 patients were on home enteral nutrition (HEN) or home parenteral nutrition (HPN) at different times (HEN n = 3865, HPN n = 626). HAN was most frequently started before the child was 3 years old and long-term HAN programs (5-9 years) were reported. The most common principal diagnosis in HEN was food-related symptoms and signs. In HPN, it was postoperative gastrointestinal disorders. A regionally differentiated prevalence of HAN patients and centers was demonstrated. Mortality among patients was 24.9% for HEN, and 9.6% for HPN, and the main in-hospital cause of death was cardiac arrest. CONCLUSIONS: HAN's use is increasing and evolving in Poland. Uneven distribution of patients and centers results in difficult access to the nutritional procedure which, together with the increasing number of patients, highlights the need for data analysis and development of nutrition centers.

Megacystis-Microcolon-Intestinal Hypoperistalsis Syndrome (MMIHS): Series of 4 Cases Caused by Mutation of ACTG2 (Actin Gamma 2, Smooth Muscle) Gene.

MMIHS, also known as Berdon's syndrome, is a rare disease that belongs to primary causes of CIPOS (chronic intestinal pseudoobstruction syndrome). Clinical characteristics of MMIHS are differential, but we come across the following classic symptoms: disorders of intestinal peristalsis, microcolon, and megacystis. In this article, we present a series of 4 patients with Berdon's syndrome, in whom we managed to identify the genetic causes of MMIHS. All infants showed clinical features of bowel obstruction and dysfunction of the urinary system after birth. Two of them also manifested disorders from other systems. The prognosis for these patients is poor, but a constant betterment of management in MMIHS, in which the leading role plays TPN (total parental nutrition), causes improvement of patients' survival.

Growth, body composition, and cardiovascular and nutritional risk of 5- to 10-y-old children consuming vegetarian, vegan, or omnivore diets.

BACKGROUND: Plant-based diets (PBDs) are increasingly recommended for human and planetary health. However, comprehensive evidence on the health effects of PBDs in children remains incomplete, particularly in vegans. OBJECTIVES: To quantify differences in body composition, cardiovascular risk, and micronutrient status of vegetarian and vegan children relative to omnivores and to estimate prevalence of abnormal micronutrient and cholesterol status in each group. METHODS: In a cross-sectional study, Polish children aged 5-10 y (63 vegetarian, 52 vegan, 72 matched omnivores) were assessed using anthropometry, deuterium dilution, DXA, and carotid ultrasound. Fasting blood samples, dietary intake, and accelerometry data were collected. RESULTS: All results are reported relative to omnivores. Vegetarians had lower gluteofemoral adiposity but similar total fat and lean mass. Vegans had lower fat indices in all regions but similar lean mass. Both groups had lower bone mineral content (BMC). The difference for vegetarians attenuated after accounting for body size but remained in vegans (total body minus the head: -3.7%; 95% CI: -7.0, -0.4; lumbar spine: -5.6%; 95% CI: -10.6, -0.5). Vegetarians had lower total cholesterol, HDL, and serum B-12 and 25-hydroxyvitamin D [25(OH)D] without supplementation but higher glucose, VLDL, and triglycerides. Vegans were shorter and had lower total LDL (-24 mg/dL; 95% CI: -35.2, -12.9) and HDL (-12.2 mg/dL; 95% CI: -17.3, -7.1), high-sensitivity C-reactive protein, iron status, and serum B-12 (-217.6 pmol/L; 95% CI: -305.7, -129.5) and 25(OH)D without supplementation but higher homocysteine and mean corpuscular volume. Vitamin B-12 deficiency, iron-deficiency anemia, low ferritin, and low HDL were more prevalent in vegans, who also had the lowest prevalence of high LDL. Supplementation resolved low B-12 and 25(OH)D concentrations. CONCLUSIONS: Vegan diets were associated with a healthier cardiovascular risk profile but also with increased risk of nutritional deficiencies and lower BMC and height. Vegetarians showed less pronounced nutritional deficiencies but, unexpectedly, a less favorable cardiometabolic risk profile. Further research may help maximize the benefits of PBDs in children.

Analysis of vitamin D3 metabolites in survivors of infantile idiopathic hypercalcemia caused by CYP24A1 mutation or SLC34A1 mutation.

Infantile hypercalcemia (IH), is a rare disorder caused by CYP24A1 or SLC34A1 variants which lead to disturbed catabolism of 25(OH)D3 and 125(OH)2D3 or increased generation of 125(OH)2D3. AIM OF STUDY: To assess the status of 2425(OH)2D3 and other markers of vitamin D in IH survivors, in whom variants of CYP24A1 or SLC34A1 gene were found and to compare these unique biochemical features with those obtained from subjects who were diagnosed in the first year of life with hypercalcemia, elevated 25(OH)D3 and low PTH but in whom neither CYP24A1 nor SLC34A1 variant was found. PATIENTS AND METHODS: 16 IH survivors in whom CYP24A1 (n = 13) or SLC34A1 (n = 3) variants were found and 41 subjects in whom hypercalcemia was diagnosed in the first year of life but in whom CYP24A1 or SLC34A1 variants were not found were included in the study. 25(OH)D3, 3-epi-25(OH)D3, 25(OH)D2, 2425(OH)2D3 were assessed by liquid chromatography coupled with tandem mass spectrometry. 125(OH)2D3 concentrations were assessed by chemiluminescence. RESULTS: Subjects with CYP24A1 variants, despite normal 25(OH)D3 levels, had higher 25(OH)D3/2425(OH)2D3 ratio values (487; 265-1073 ng/mL) when compared to subjects with SLC34A1 variants (16; 16-23 ng/mL) and with subjects in whom CYP24A1 or SLC34A1 were not found (56; 9-56 ng/mL) (p = 0.00003). Separation of interfering metabolite further increased differences between subjects with and without CYP24A1 mutation. CONCLUSIONS: Survivors of IH with CYP24A1 variant, despite being normocalcemic, still presented extremely high 25(OH)D3/2425(OH)2D3 ratio values. Separation of interfering compound further increased differences between subjects with CYP24A1 mutation and without this mutation.

Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations.

BACKGROUND: Infantile hypercalcaemia (IH) is a vitamin D3 metabolism disorder. The molecular basis for IH is biallelic mutations in the CYP24A1 or SLC34A1 gene. These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations). The incidence rate of IH in children and the risk level for developing end-stage renal disease (ESRD) are still unknown. The aim of this study was to analyse the long-term outcome of adolescents and young adults who suffered from IH in infancy. DESIGN: Forty-two children (23 girls; average age 10.7 ± 6.3 years) and 26 adults (14 women; average age 24.2 ± 4.4 years) with a personal history of hypercalcaemia with elevated 1,25(OH)2D3 levels were included in the analysis. In all patients, a genetic analysis of possible IH mutations was conducted, as well as laboratory tests and renal ultrasonography. RESULTS: IH was confirmed in 20 studied patients (10 females). CYP24A1 mutations were found in 16 patients (8 females) and SLC34A1 in 4 patients (2 females). The long-term outcome was assessed in 18 patients with an average age of 23.8 years (age range 2-34). The average glomerular filtration rate (GFR) was 72 mL/min/1.73 m2 (range 15-105). Two patients with a CYP24A1 mutation developed ESRD and underwent renal transplantation. A GFR <90 mL/min/1.73 m2 was found in 14 patients (77%), whereas a GFR <60 mL/min/1.73 m2 was seen in 5 patients (28%), including 2 adults after renal transplantation. Three of 18 patients still had serum calcium levels >2.6 mmol/L. A renal ultrasound revealed nephrocalcinosis in 16 of 18 (88%) patients, however, mild hypercalciuria was detected in only one subject. CONCLUSIONS: Subjects who suffered from IH have a greater risk of progressive chronic kidney disease and nephrocalcinosis. This indicates that all survivors of IH should be closely monitored, with early implementation of preventive measures, e.g. inhibition of active metabolites of vitamin D3 synthesis.