Band 36, Heft 8

Objectives Metabolic syndrome (MetS) is a cluster of conditions linked to obesity that increases cardiovascular risk. We evaluated the frequency of clinical abnormalities associated with overweight and obesity in childhood, to determine whether a diagnosis of MetS is appropriate in this population. Methods Cross-sectional study with 116 pubertal and prepubertal children with a mean age (SD) of 10.9 (2.5) years, with overweight and obesity. We defined MetS using the International Diabetes Federation criteria, regardless of the age. Results 45 patients met the criteria, 20 had at least one metabolic abnormality in addition to a high waist circumference (WC), and seven with WC below percentile 90th, had at least one metabolic abnormality. The prepubertal had higher zBMI [3.1 (2.6–3.8) vs. 2.8 (2.4–3.3); p=0.037], less lean body mass (kg) [27.13 (7.3) vs. 34.13 (9.8); p=0.005] and a similar frequency of non-alcoholic fatty liver disease (NAFLD) compared to the pubertal [44.7 vs. 35.9; p=0.323]. Prepubertal with NAFLD had higher zBMI, lower HDL levels, higher TG/HDL ratios and higher fat percentages; while pubertal with NAFLD had higher WC/height, aspartate aminotransferase and oxaloacetic transaminase. Conclusions The diagnosis of MetS in childhood is not fundamental. Individualized management, focusing on the earliest age groups, in which we identified a more severe degree of obesity, should be done. We also recommend screening for NAFLD in all ages, due to the high prevalence observed.

Objectives Case reports show hypertension in children treated with GnRH analogues for central precocious puberty (CPP). However, relevant data on blood pressure are scarce. We aimed to evaluate blood pressure (BP) among girls with idiopathic CPP and early-onset puberty before and during GnRH analogue therapy; and to examine associations of blood pressure with clinical parameters. Methods For this retrospective longitudinal cohort study, demographic, anthropometric, clinical, and laboratory data were collected from electronic files. The study group included 112 girls with idiopathic CPP or early-onset puberty followed in a tertiary pediatric endocrinology institute, and a control group of 37 healthy pre-pubertal girls. The main outcome measures were BP percentile, before, and during treatment with GnRH analogue. Results At baseline, similar proportions of the study and control groups had BP values>90th percentile: 64 (53 %) and 17 (46 %), respectively (p=0.57). The mean systolic and diastolic BP percentiles measured under treatment remained unchanged. In the study group, baseline BP>90th percentile compared to normal baseline BP was associated with lower birthweight and a higher body mass index-standard deviation score: 2,821 ± 622 vs. 3,108 ± 485 g and 1.0 ± 0.7 vs. 0.70 ± 0.8, respectively, p=0.01 for both. Conclusions GnRH analogue therapy for precocious or early puberty was not associated with increased blood pressure. The stability of mean blood pressure percentile during treatment is reassuring.

Objectives We sought to study factors predictive of achieving menstrual suppression with norethindrone vs. norethindrone acetate in adolescents, as optimal dosing is unknown. Secondary outcomes included analyzing prescriber practices and patient satisfaction. Methods We performed a retrospective chart review of adolescents ages <18 years presenting to an academic medical center from 2010 to 2022. Data collected included demographics, menstrual history, and norethindrone and norethindrone acetate use. Follow-up was measured at one, three, and 12 months. Main outcome measures were starting norethindrone 0.35 mg, continuing norethindrone 0.35 mg, achieving menstrual suppression, and patient satisfaction. Analysis included Chi-square and multivariate logistic regression. Results Of 262 adolescents initiating norethindrone or norethindrone acetate, 219 completed ≥1 follow-up. Providers less often started norethindrone 0.35 mg for patients with body mass index ≥25 kg/m 2 , prolonged bleeding, or younger age at menarche, but more often for patients who were younger, had migraines with aura, or were at risk of venous thromboembolism. Those with prolonged bleeding or older age at menarche were less likely to continue norethindrone 0.35 mg. Obesity, heavy menstrual bleeding, and younger age were negatively associated with achieving menstrual suppression. Patients with disabilities reported greater satisfaction. Conclusions While younger patients more often received norethindrone 0.35 mg vs. norethindrone acetate, they were less likely to achieve menstrual suppression. Patients with obesity or heavy menstrual bleeding may achieve suppression with higher doses of norethindrone acetate. These results reveal opportunities to improve norethindrone and norethindrone acetate prescribing practices for adolescent menstrual suppression.

Objectives Central precocious puberty (CPP) is one of the common reasons for referral to pediatric endocrinology. Magnetic resonance imaging (MRI) is used to rule out intracranial pathologies. However, there is insufficient information in the literature about bone marrow abnormalities on MRI in CPP cases. The aim of this study was to evaluate the apparent diffusion coefficient (ADC) values obtained from bone marrow diffusion weight images (DWI) of cranial bone structures and the status of sphenooccipital synchondrosis (SOS) in CPP. Methods MRI data from 6-to 9-year-old girls with CPP and a healthy control group were evaluated. Anthropometric data, FSH, LH, and oestradiol tests were recorded, and the relationship between SOS status, DWI-ADC values of the clivus, parietal bone, and occipital protuberance were compared. Results The study included 146 girls, 79 CPP, and 67 healthy aged 6–9 years (median: 8 (2)). The diagnosis age was 8.30 ± 0.8 years. The ADC values were significantly lower on CPP than normal controls (p=<0.05). In the CPP group, pattern 1 was found at 2 % (n=2), pattern 2 at 3.5 % (n=3), and pattern 3 at 3.5 % (n=3) in clivus sphenooccipital synchondrosis. There was no correlation between the mean parietal, occipital, and clivus ADC values and any variable (p>0.05). Conclusions DWI-MRI ADC analysis can be used as a quantitative radiological marker for early detection of CPP, even before changes in sphenooccipital synchondrosis.

Objectives Severe 25-hydroxyvitamin D (25(OH)D) deficiency can result in life-threatening presentations due to hypocalcemia leading to seizures and cardiac arrhythmias. vitamin D deficiency is a common cause of hypocalcemia and rickets in children; however, there are no recent studies on the burden of inpatient admissions in the United States. Our study aims to describe the clinical characteristics and risk factors of inpatient admissions due to severe hypocalcemia and 25(OH)D deficiency at a freestanding academic children’s hospital. Methods A descriptive retrospective chart review was completed on all inpatient admissions from 2016 to 2021 for children 0–18 years of age with corrected calcium <8 mg/dL and 25(OH)D <10 ng/mL during admission. Results Thirty-eight patients met the inclusion criteria (74 % Black/African American). Neurological signs described in 49 %, bone abnormalities in 17 % and EKG abnormalities in 42 % of the patients. The mean calcium serum level was 6.0 mmol/L (range 5.0–7.9 mmol/L), the mean iCa 0.77 mmol/L (range 0.54–0.99 mmol/L). The mean level of 25(OH)D was 5.5 ng/mL (range 2.1–9.7 ng/mL). The median length of stay was 4.5 (range 1–59 days). Conclusions In this retrospective observational study, risk factors identified: (1) Black/African American race (2) age less than two years (3) lack of supplementation of vitamin D and (4) dietary restrictions. Inpatient admissions are preventable through the implementation of education at the community and healthcare levels.

Objectives The aim of this study was to evaluate the early pregnancy exposure of maternal triglyceride (mTG) and its effects on birth weight, which was an important indicator for nutritional status of newborns, and even its long-term health. Methods A retrospective cohort study was designed to investigate the relationship between mTG in early pregnancy and birth weight. Totally 32,982 women who had a singleton pregnancy and underwent serum lipids screening during early pregnancy were included in this study. Logistic regressions were used to evaluate the correlations between mTG levels and small for gestational age (SGA) or large for gestational age (LGA), and the restricted cubic spline models were applied to explore the dose-response relationship. Results The increased mTG levels during early pregnancy decreased the risk of SGA and increased the risk of LGA. The high mTG (>90th, 2.05 mM) was showed associated with higher risk of LGA (AOR, 1.35; 95 %CI, 1.20 to 1.50), and lower risk of SGA (AOR, 0.78; 0.68 to 0.89). Lower risk of LGA (AOR, 0.81; 0.70 to 0.92) was found in those cases of low mTG (<10th, 0.81 mM), but no correlation was found between low mTG levels and the risk of SGA. The results remained robust after excluding women with high or low body mass index (BMI) and pregnancy complications. Conclusions This study suggested that early pregnancy exposure of mTG were related to the occurrence of SGA and LGA. mTG levels higher than 2.05 mM (>90th) were suggested to be avoid because of its risk for LGA, while mTG lower than 0.81 mM (<10th) showed its benefits for ideal birthweight range.

Objectives To study the biochemical, clinical and molecular characteristics of 5,10- methylenetetrahydrofolate reductase (MTHFR) deficiency in Pakistani patients from a single center. Methods Medical charts, urine organic acid chromatograms, plasma methionine and Hcys levels, and molecular testing results of MTHFR gene of patients presenting at the Biochemical Genetics Clinic, AKUH from 2016 to 2022 were reviewed. Results Neonatal MTHFR deficiency was found in five patients. The median (IQR) age of symptom onset and diagnosis were 18 (8.5–22) and 26 (16.5–31) days. The median lag between symptom onset and diagnosis was 8 (4.5–12.5) days. The median age of treatment initiation and duration of treatment were 26 (16.5–49) and 32 (25.5–54) days. The most common clinical features were lethargy, poor feeding, and seizures. The MTHFR gene sequencing revealed homozygous variants p.K510K, p.R567*, and p.R157W. Renal insufficiency manifesting as elevated serum creatinine and responding to betaine therapy was noted in one patient. This has not been previously reported in neonatal MTHFR deficiency and may reflect engagement of alternate pathways of remethylation. Adult onset MTHFR deficiency was found in six patients, with a heterogeneous neurological presentation. The median lag between symptoms onset and diagnosis was 7 (3–11) years. MTHFR gene sequencing revealed homozygous variant p.A195V in five patients from one family and p.G261V in the other. Two of the five reported variants are novel that include p.R157W and p.G261V. Conclusions Eleven patients of this rare disorder from a single center indicate the need for clinical awareness and appropriate biochemical evaluation to ensure optimal outcomes.

Objectives Congenital hypothyroidism (CH) is a decrease in thyroid hormone function in newborns, being one of the leading causes of neurological deficits and long-term metabolic complications. This study aims to determine the prevalence and characteristics of CH cases in Bogotá, Colombia, between 2015 and 2021, as notified through the mandatory report to the Public Health Surveillance System (PHSS). Methods A retrospective cross-sectional study was conducted. All live births (LB) with a weight ≥500 g, diagnosed with CH with or without goiter (ICD-10 codes E030 and E031, respectively) in Bogotá during 2015–2021 were analyzed. Results For a total of 201 cases, the prevalence rate was 3.29 cases per 10,000 LB. 92.54 % were classified as isolated cases of CH, 4.48 % syndromic, and 2.98 % polymalformated. A total of 16.92 % was small for gestational age. The mean gestational age was 37.38 weeks (SD 2.76), 26.87 % were preterm births. Among the mothers, 8.96 % suffered from pregnancy-related or chronic diseases, the most common being hypertensive disorders of pregnancy and pre-existant hypothyroidism (without clarity concerning etiology). A total of 66.67 % of cases did not receive treatment after diagnosis. Treatment was established by an average age of 27 days after birth (SD 36.02) and 17 days after case notification to the PHSS (SD 36.13). Conclusions Observed prevalence is similar to the rate reported by health authorities in Colombia but inferior to reports from high-income countries, highlighting the importance of improvements in the Colombian LB’s screening program. Time to diagnosis and treatment was observed to be prolonged, suggesting that new pathways are required for timely CH treatment.

Objectives Mitochondrial diabetes mellitus is caused by dysfunctional mitochondria and is often misdiagnosed because of its various clinical manifestations. It’s even rarer in children, and without a clear family history of diabetes with hearing loss, it’s often difficult to diagnose. Case presentation This is a case study of a family with maternally inherited diabetes mellitus and deafness (MIDD). The proband was an adolescent girl with diabetes with a family history of type 2 diabetes (T2DM) for three generations. Family members have undetected hearing impaired. The proband could not be diagnosed with type 1 diabetes (T1DM) or T2DM. Therefore, whole exome and mitochondrial gene sequencing was performed, which identified an m.3243A>G mutation in the mitochondrial DNA. Conclusions This suggests that we should be alert to the possibility of hereditary diabetes, especially mitochondrial diabetes in patients with atypical diabetes. A thorough physical examination is very important. What is new: (1) Mitochondrial diabetes in childhood may not be accompanied by deafness even with highly heteroplasmy levels. (2) In MIDD patients, sometimes hearing loss cannot be perceived, which requires us to conduct detailed physical examinations and related examinations. (3) The use of metformin in MIDD patients did not have adverse consequences.

Objectives To present a case of a new pathogenic variant of DICER1. Case presentation 13-year-old female with non-toxic multinodular goiter and ovarian Sertoli–Leydig cell tumor, in whom a pineal parenchymal tumor of intermediate differentiation was diagnosed. Next-generation sequencing revealed a new germline mutation in the DICER1 gene (exon 16, c2488del [pGlu830Serfs*2] in heterozygosis), establishing the diagnosis of DICER1 syndrome. Conclusions Mutations in the DICER1 gene cause genetic predisposition to a wide spectrum of benign or malignant tumors from childhood to adulthood.

Objectives The role of serum fibroblast growth factor 23 (FGF23) level in early neonatal period on the diagnosis of X-linked hypophosphatemic rickets (XLH) remains unclear. Case presentation Two female patients from the first pedigree had an affected mother, and the other female from the second pedigree had an affected father. In all three cases, FGF23 levels were high in cord blood and peripheral blood at day 4-5. Additionally, the FGF23 levels considerably increased from birth to day 4-5. We identified a PHEX pathogenic variant and initiated treatment during infancy in each case. Conclusions In neonates with a parent diagnosed as PHEX -associated XLH, FGF23 in cord blood and peripheral blood at day 4-5 may be useful markers for predicting the presence of XLH.

Objectives DNAJC12 deficiency (OMIM# 617384) is a new cause of hyperphenylalaninemia (HPA). The deficiency of the co-chaperone protein DNAJC12 was identified in 2017. To date, only 43 patients have been reported. Here, we report four patients from a single family with DNAJC12 deficiency while being followed up with a diagnosis of HPA. Case presentation Two of the patients, who were cousins, were diagnosed with HPA by newborn screening. And the other two patients were siblings of these patients. Neurological examinations were normal except for one patient with mild learning disability. A c.158-2A>T p.(?) biallelic pathogenic variant was detected in intron 2 of the DNAJC12 gene. In the 24 h tetrahydrobiopterin (BH4) challenge test, there was a significant decrease in phenylalanine levels, especially at the 16th hour. Three patients had decreased homovalinic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in cerebrospinal fluid (CSF), while only one had decreased 5HIAA. In treatment, sapropterin, levodopa/carbidopa and 5-OH tryptophan were started. Conclusions We propose that it will be beneficial to evaluate the patients who have unexplained hyperphenylalaninemia for DNAJC12 deficiency. Patients with early diagnosis of neurotransmitter deficiency may be given a chance to be treated before clinical symptoms begin.

Objectives The 12q14 microdeletion syndrome is a rare genetic condition characterized by intrauterine growth restriction, proportionate short stature, failure to thrive, and intellectual disability. Few reports have discussed the therapeutic aspect of patients with 12q14 microdeletion syndrome. Herein, we report the first case of 12q14 microdeletion patient treated with rhGH without growth hormone deficiency. Case presentation The patient presented with feeding difficulties during infancy, failure to thrive, intellectual disability and subtle dysmorphic facial features. The patient first visited the clinic at 5 years and 3 months, his height was 91.4 cm (−4.9 SD) and weight 10.0 kg (−2.86 SD). The growth hormone level was within the normal range. Bone radiological testing revealed no significant abnormalities. Genetic analysis identified a 6.97 Mb deletion at the chromosome 12q14.1–q14.3 region in the proband. Recombinant human growth hormone therapy was initiated, which lasted for 12 months, and the new height was 101.0 cm (−4.0 SD) and weight 12.0 kg (−3.6 SD). Conclusions This report first showed that patient with 12q14 microdeletion, although without growth hormone deficiency, can benefit from human growth hormone therapy.

Objectives CHI is a relevant cause of persistent and severe hypoglycemia and the ABCC8 gene mutation is one of most common cause of the disease. Two main types of CHI have been described, diffuse and focal form. Octreotide is a medication utilized in case of diazoxide-unresponsive forms of CHI. For those CHI focal forms where is decided either to manage medically or until resolutive surgery is completed, octreotide can be administered as subcutaneous injection or as continuous subcutaneous infusion via insulin pump. However, it is unclear how to adjust the drug’s daily basal pattern when a pump is used. Case presentation We present a case of an infant with a diazoxide-unresponsive focal form of CHI, due to ABCC8 mutation ABCC8, treated with octreotide. To better evaluate the glycemic trend, a CGM was placed. In order to achieve a better personalization of the therapy we utilized an insulin pump for octreotide administration. Conclusions The adoption of the CGM and insulin pump, allowed a better personalization of the therapy and a reduction of acute carbohydrate intake, promoting a good auxological growth before resolutive surgery. What is new? Octreotide administered with an insulin pump in patient with CHI allows a wide modulation of the daily therapy. The CGM allows a continuous and a less painful control of the glycemic trend in a patient with CHI. Different basal rates, given via insulin pump may allow a better personalization of the therapy. Prevention of hypoglycemia reduces the acute introduction of carbohydrates, promoting normal growth..