Volume 36, Issue 9

Glycogen storage disease (GSD) type 1a is an inherited autosomal recessive metabolic disease caused by a deficiency in glucose-6-phosphatase activity. The objectives of this research were to systematically review the published literature on the epidemiology of GSD 1a and to assess the performance of reported epidemiology measures in a simulation model. In this systematic literature review 2,539 record titles and abstracts were screened. Of these, only 11 studies contained relevant data on GSD 1a disease epidemiology. Reported disease frequency ranged from 0.085/100,000 to 10.3/100,000 newborns when considering all the GSD literature. When this was narrowed to GSD 1 and GSD 1a, the range was tightened to 0.25–3.02/100,000 and 0.085–4.9/100,000 newborns, respectively. Most of the identified studies counted the number of diagnoses in a defined period and related to the number of births in the same (Dx method) or different time period (DoB method). The simulation model results indicate that in most of the situations, the Dx method provides a closer estimate to the true disease incidence than the DoB method. Despite the scarcity of epidemiology data, the results of this systematic review strongly support that GSD 1a and its parent disease groups (GSD and GSD 1) are rare diseases.

Objectives We aimed to analyse weight change and risk factors associated with excessive weight gain in preschool children during the COVID-19-related lockdown in western China. Methods A retrospective observational study of eight randomly selected kindergartens was conducted. Data was collected via online electronic questionnaires during the lockdown. Results During the COVID-19 lockdown period, the incidence of overweight and obesity among preschool children involved in the study was 7.6 and 14.7 %, respectively. In addition, the incidence of obesity among children aged 3–4 years was 26.3 %, which was higher than that of other age groups. Children with excessive weight gain (weight gain ≥1.0 kg) spent more time on TV and video viewing during lockdown than children with normal gain. Among children with excessive weight gain, weight before lockdown and fathers’ BMI were higher than those of children with normal weight gain. Heavier weight before lockdown (OR 1.044, p<0.05), higher father’s BMI (OR 1.022, p<0.05), fresh fruit consumption during lockdown (frequently, ≥5 times/week) (OR 5.946, p<0.05), and long touch-screen device time during lockdown (OR 1.259, p<0.05) were found to be risk factors significantly associated with excessive weight gain. Living space (80–100 m 2 , OR=0.499, p<0.05; 100–150 m 2 , OR=0.467, 95 % CI 0.26, 0.83) and good mental behavior during the lockdown (OR=0.056, p<0.05) were found to be significant protective factors against excessive weight gain. Conclusions There was a clear trend in excessive weight gain among preschool children during the COVID-19 lockdown, especially those who had already had heavier weight before the pandemic. The obesity-promoting environment resulting from the COVID-19 pandemic may lead to a further serious exacerbation of the childhood obesity pandemic. Therefore, child health care providers must pay close attention to this and implement effective preventive measures in a timely manner.

Objectives The aim of our study was the longitudinal assessment of bone health index (BHI) in short-statured children during growth hormone (GH) treatment to estimate changes in their bone health. Methods 256 short-statured children (isolated GH deficiency (IGHD) n=121, multiple pituitary hormone deficiency (MPHD) n=49, intrauterine growth retardation (small for gestational age (SGA)) n=52, SHOX (short stature homeobox gene) deficiency n=9, Ullrich Turner syndrome (UTS) n=25) who started with GH between 2010 and 2018 were included. Annual bone ages (Greulich and Pyle, GP) and BHI were, retrospectively, analysed in consecutive radiographs of the left hand (BoneXpert software) from GH therapy start (T0) up to 10 years (T10) thereafter, with T max indicating the individual time point of the last available radiograph. The results are presented as the median (25 %/75 % interquartile ranges, IQR) and statistical analyses were performed using non-parametric tests as appropriate. Results The BHI standard deviation scores (SDS) were reduced (−0.97, −1.8/−0.3) as bone ages were retarded (−1.6 years, −2.31/−0.97) in all patients before start of GH and were significantly lower in patients with growth hormone deficiency (GHD) (−1.04, −1.85/−0.56; n=170) compared to non-GHD patients (−0.79, −1.56/−0.01; n=86; p=0.022). BHI SDS increased to −0.17 (−1/0.58) after 1 year of GH (T1, 0.5–1.49, p<0.001) and to −0.20 (−1/−0.50, p<0.001) after 5.3 years (T max, 3.45/7.25). Conclusions BHI SDS are reduced in treatment-naive short-statured children regardless of their GH status, increase initially with GH treatment while plateauing thereafter, suggesting sustained improved bone health.

Objectives Early diagnosis of childhood growth disorders, their timely and proper treatment are important for better outcomes.The aim of the present study was to assess the results of the first 18 months of the growth disorders related twinning programme “Partners4Growth” implemented at all tertiary university pediatric endocrinology clinics in Bulgaria. Methods In 2019, Partners4Growth started operation at 7 centres (4 experienced and 3 twin centres) with the main aim of aligning their practices in the shortest possible time. Education of twin centres’ personnel was organized, equipment and methods for growth evaluation and follow-up were standardized. The approach was tested initially at one centre. At baseline and at the 18th month a questionnaire concerning diagnosis and management of recombinant human growth hormone (rhGH) requiring disorders was applied. Results A total of 104 new patients were diagnosed compared to 30 in the previous year. Of those, 91 started rhGH treatment – 65 (64 %) GH deficient, 12 (12 %) Turner syndrome, 7 (7 %) Prader–Willi syndrome patients, and 7 (7 %) born small for gestational age without postnatal catch-up, representing 35.8 % of all currently rhGH treated Bulgarian children. A better geographical coverage and more advanced diagnostic and management practices were achieved. Conclusions Partners4Growth facilitated the alignment of the tertiary pediatric endocrinology centres competences thus leading to an improved diagnosis and treatment of growth disorders as well as better patients’ access. For its short existence, the Programme increased significantly the number of new patients in the difficult times of COVID-19 pandemic thus justifying its continuation.

Objectives Most small for gestational age (SGA) infants show catch-up growth but the minority who do not may benefit from growth-promoting treatment. We determined the prevalence of, and risk factors for, failure to show catch-up growth in term SGA infants. Methods Prospective observational study of infants born at 37–42 weeks gestation between December 2012 and March 2014 with birth weight <10th percentile. Length, weight and head circumference were measured from birth to 2 years. Results Of 457 (3.9 %) term infants with SGA, 446 (97.6 %) were followed up until 2 years. At 24 months, supine length, weight and head circumference were ≥−2 standard deviation score (SDS) in 87.9 , 96.4 and 97.1 % subjects, with persistent short stature in 12.1 %. In a multivariate analysis, the independent predictors of failure to show catch-up growth at 24 months were: maternal height <150 cm, difference between mid-parental height and birth length of ≥2.2 SDS, height at 24 months <–2 SDS below mid-parental height SDS, history of SGA, ponderal index <3rd centile and duration of breast feeding <3 months. Conclusions This study provides data concerning the epidemiology of SGA in Algeria and the factors associated with post-natal growth. Establishing which children remain short at 2 years has identified a cohort of patients requiring continuing follow up, with a view to instituting growth hormone therapy in selected cases. These results favour the setting up of an integrated national program to register SGA infants at birth, with re-evaluation at 2 years. (250 words).

Objectives Understanding the normal range of laboratory values as pertained to different age groups and males or females is paramount in health care delivery. We aimed to assess the distribution of morning fasting serum glucose levels by age and sex in the general population of children using a large-scale population-based cohort. Methods A retrospective study with real-world de-identified data from a large, state mandated health fund in Israel among children aged 2–18 years old between 2006 and 2019. Age, sex, and BMI differences in mean glucose levels were evaluated. Results Study included 130,170 venous blood samples from 117,411 children, 53.3 % were female. After adjusting for age boys had higher fasting serum glucose levels than girls, with a mean of 89.21 ± 8.66 mg/dL vs. 87.59 ± 8.35 (p<0.001) [4.95 ± 0.48 mmol/L vs. 4.86 ± 0.46]. Compared to the 15 to 18 year-olds (88.49 ± 7.63 mg/dL) [4.92 ± 0.42 mmol/L], 2 to 5 year-olds had lower glucose levels (84.19 ± 10.65, [4.68 ± 0.59] (p<0.001)), 11 to 14 year-olds had higher glucose (90.40 ± 7.42 [5.02 ± 0.41], (p<0.001)) and 6 to 10 year-olds showed no difference (88.45 ± 8.25) [4.91 ± 0.46]. 33.0 % (n=42,991) had a BMI percentile record the same year as their glucose test result. There was a weak yet significant positive association between blood glucose levels and BMI. Conclusions Our large cohort indicates that boys have slightly higher fasting serum glucose levels than girls, as do adolescents compared to younger children. This finding is important for the delivery of adequate health care, screening for illness and avoiding unnecessary investigations and tests.

Objectives This study aims to investigate the prevalence of overweight and obesity in preschool children in Hangzhou and assess the impact of childcare management. By examining the characteristics and predicting the trends of overweight and obesity, we hope to emphasize the significance of childcare management in primary community health service centers and the use of Electronic Health-care System in kindergartens. This study also seeks to provide evidence for intervention measures and effective prevention and control management of childhood obesity. Methods From 2020 to 2022, kindergarten children aged 3–6 years old were selected as the research objects in kindergartens in Hangzhou. The Electronic Health-care System will be utilized to facilitate the management of childhood obesity and provide guidance and training to pediatricians and Primary Care Physicians. Results The overall detection rates of overweight and obesity were 7.27 % and 3.55 %, respectively, among children aged 3–6 years in Hangzhou. The rates of simple obesity in Hangzhou preschool children aged 3–6 years were 4.25 , 3.42, and 3.04 % from 2020 to 2022, respectively; the overweight detection rates of children were 8.27 , 7.28, and 6.34 %, respectively, and the difference was statistically significant (p<0.05). The detection rates of overweight and obesity in 2022 were significantly lower than those in 2020 (p<0.05). The prevalence of obesity in children increased with age. Boys had a significantly higher incidence rate of obesity than girls (p<0.05). The proportion of children with moderate and severe obesity showed a downward trend. Intervention measures for childhood obesity in primary community health service centers and kindergartens are constantly being implemented. Conclusions The prevalence of obesity in preschool children aged 3–6 years in Hangzhou exhibited a decreasing tendency. This research has identified that child care administration, particularly the implementation of the Electronic Health-care System, demonstrates effectiveness in handling overweight and obesity amongst children.

Objectives While the positive correlation was shown in a few studies which investigated the relationship between obesity and pentraxin-3 (PTX-3) levels, different findings were obtained in other studies. We aimed to determine PTX-3 levels in obese and healthy children, and their relationship with Metabolic Syndrome (MetS) criteria. Methods 105 children and adolescents were considered as the study population. Participants were divided into three groups; obese and MetS (OM+), obese and non-MetS (OM-) and the control group. Fasting glucose, blood lipids and PTX-3 levels were measured. Ultrasonography was performed to detect hepatic steatosis. MetS and hepatic steatosis were investigated by dividing the patients into two groups according to PTX-3 levels. Results The study population consisted of 37 patients with OM+; 35 patients with OM- and 33 healthy children. OM+ patients had higher fasting insulin (p<0.001), homeostatic model assessment for insulin resistance (p<0.001), triglyceride (p<0.001) and lower high-density lipoprotein (p=0.001). The PTX-3 level was higher in the OM+ group compared to both OM- group and the control group (p=0.002). When two groups were generated according to PTX-3 level, a higher frequency of MetS was detected in the high PTX 3 group than in all three major MetS diagnostic criteria groups. Moreover, there was more hepatic steatosis in the high PTX-3 group independent from obesity and MetS. Conclusions Higher PTX-3 levels were present in children and adolescent obese patients with MetS.

Objectives Carbamoyl phosphate synthetase 1 (CPS1) deficiency is a severe urea cycle disorder. Patients can present with hyperammonemic coma in the first days of life. Treatment includes nitrogen scavengers, reduced protein intake and supplementation with L-arginine and/or L-citrulline. N-carbamoyl glutamate (NCG) has been hypothesized to stimulate the residual CPS1 function, although only few patients are reported. Case presentation We report a patient with neonatal-onset CPS1 deficiency who received NCG in association with nitrogen scavenger and L-citrulline. The patient carried the novel variants CPS1 -c.2447A>G p.(Gln816Arg) and CPS1 -c.4489T>C p.(Tyr1497His). The latter is localized in the C-terminal allosteric domain of the protein, and is implicated in the binding of the natural activator N-acetyl-L-glutamate. NCG therapy was effective in controlling ammonia levels, allowing to increase the protein intake. Conclusions Our data show that the response to NCG can be indicated based on the protein structure. We hypothesize that variants in the C-terminal domain may be responsive to NCG therapy.

Objectives Proximal renal tubular acidosis (pRTA) is characterized by a defect in the ability of the proximal convoluted tubule to reabsorb bicarbonate. The biochemical hallmark of pRTA is hyperchloremic metabolic acidosis with a normal anion gap, accompanied by appropriate acidification of the urine (simultaneous urine pH <5.3). Isolated defects in bicarbonate transport are rare, and pRTA is more often associated with Fanconi syndrome (FS), which is characterized by urinary loss of phosphate, uric acid, glucose, amino acids, low-molecular-weight proteins, and bicarbonate. Children with pRTA may present with rickets, but pRTA is often overlooked as an underlying cause of this condition. Case presentation We report six children with rickets and short stature due to pRTA. One case was idiopathic, while the remaining five had a specific underlying condition: Fanconi-Bickel syndrome, Dent's disease, nephropathic cystinosis, type 1 tyrosinemia, and sodium-bicarbonate cotransporter 1-A (NBC1-A) defect. Conclusions Five of these six children had features of FS, while the one with NBC1-A defect had isolated pRTA.

Objectives To emphasize the significance of genetic mutations in idiopathic infantile hypercalcemia and the potential therapeutic effectiveness of zoledronic acid in managing hypercalcemia attributed to gene mutations. Case presentation A 1-year-old female infant was referred to our hospital. The patient developed hypercalcemia despite no vitamin D prophylaxis or intake. In the acute phase, conventional calcium-lowering treatments showed limited efficacy, while the administration of zoledronic acid demonstrated effectiveness in controlling hypercalcemia. Subsequently the patient maintained normal calcium levels via a low-calcium diet and avoiding vitamin D intake. Genetic testing confirmed a homozygous mutation (c.476G>C) in the CYP24A1 gene. Conclusions Family screening and genetic counseling are crucial for early detection and prevention of hypercalcemia. This case emphasizes the importance of genetic mutations in disease development and the potential therapeutic efficacy of zoledronic acid in managing hypercalcemia attributed to gene mutations.

Objectives To highlight important clinical aspects of Persistent Müllerian duct syndrome (PMDS). PMDS belongs to the group of differences of sex development. It is attributed to mutations in genes encoding for the anti-Müllerian hormone or its type II receptor (AMHR2) and inherited via an autosomal recessive transmission. Case presentation An 18-day-old male infant with known bilateral cryptorchidism, presented with left-sided obstructed inguinal hernia. The diagnosis of PMDS was considered during inguinal exploration as both testes together with uterus and fallopian tubes were recognized in the hernial sac. Histology confirmed the presence of Müllerian-derived tissues. Genetic testing revealed two different mutations of the AMHR2 gene, both with autosomal recessive transmission: a frequently encountered deletion of 27 pairs bases on exon 10 of this 11 exon gene and a novel deletion of 2 pairs bases on exon 6. Conclusions This case is notable being the rarest type of PMDS, that of transverse testicular ectopia and associated with a novel AMHR2 gene mutation.

Objectives Hypothalamic hamartoma (HH) typically presents with gonadotrophin-dependent precocious puberty and/or seizures. Other endocrine disturbances are rare. We describe an infant with syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) and a HH. Case presentation A 6-week-old infant presented with seizures and life-threatening hyponatremia. A HH was identified on magnetic resonance imaging. Clinical examination and biochemistry were consistent with SIADH, and serum copeptin was high during hyponatremia, further supporting this diagnosis. Tolvaptan was effective in normalizing plasma sodium and enabling liberalization of fluids to ensure sufficient nutritional intake and weight gain and manage hunger. Conclusions Hyponatremia due to SIADH is novel at presentation of a HH, and can be challenging to diagnose and manage. Successful management of hyponatremia in this case was achieved using tolvaptan.