Journal of Pediatric Endocrinology & Metabolism最新文献

Objectives: Tangier disease (TD) is a rare autosomal recessive condition characterized by high-density lipoprotein (HDL) deficiency; involving symptoms of polyneuropathy, hyperplastic orange-yellow tonsils, vision disorder, and sudden cardiac death. The major clinical symptoms of TD may not all be co-present. This study evaluates patients diagnosed with TD in childhood to improve the possibility of early diagnosis of asymptomatic cases by reporting our patients' clinical characteristics in order to minimize delayed diagnosis and emphasize the importance of TD, easily detected by HDL measurement.

Methods: This retrospective and cross-sectional study investigated seven patients from three different families diagnosed with TD.

Results: Four of seven patients were girls. Median age was 5.7 years at symptom onset and 6.5 years at diagnosis. The index case presented with neuropathy findings, and TD was diagnosed based on genetic analysis. Low lipid levels were determined in a sibling and cousins with cardiac death and gait disturbance in the family. TD was confirmed by genetic investigation. Our other patients were evaluated due to anemia, thrombocytopenia, yellow-orange hypertrophy in the tonsils, and organomegaly. Diagnosis was established with genetic analysis and low HDL. No coronary artery disease or ocular involvement was observed in any case.

Conclusions: All patients presenting with neuropathy and gait disorders should undergo detailed tonsil examinations and HDL tests. Genetic analysis should be carried out if necessary. Family screening should be recommended to patients with consanguineous marriages after diagnosis of TD.

Objectives: HSD3B7 deficiency is a genetic disorder caused by mutations in the HSD3B7 gene, leading to impaired bile acid synthesis and the accumulation of toxic intermediates. Affected patients typically present with cholestatic liver disease, including jaundice and progressive liver dysfunction.

Case presentation: This case series describes three pediatric patients from two families diagnosed with HSD3B7 deficiency, each demonstrating varying clinical severity and outcomes. All cases exhibited cholestasis with normal GGT levels and elevated AST/ALT. Case 1, a male infant, also presented with craniosynostosis and failure to thrive, responding well to cholic acid therapy. Case 2, a female infant and first cousin of Case 1, had mild cardiac abnormalities and showed slight improvement with ursodeoxycholic acid and vitamin supplementation. Case 3, a male infant with a compound HSD3B7 and ATP8B1 mutation, progressed to fulminant liver failure, ultimately requiring a liver transplant. A novel c.531 + 1G>C variant was identified in Cases 1 and 2, contributing to understanding genotype-phenotype correlations in bile acid synthesis disorders.

Conclusions: Early diagnosis and treatment with bile acid therapy are crucial for improving outcomes, although some cases may necessitate liver transplantation. This series emphasizes the need to consider bile acid synthesis disorders in the differential diagnosis of cholestasis.

Objectives: Premature ovarian insufficiency (POI) affects 1 in 10,000 children, with its molecular causes largely unknown. Adult studies suggest that low androgen levels induce ovarian insufficiency, but data on about this in children is limited. This study aims to assess the prevalence of low androgen levels in childhood POI and its relationship with adrenal insufficiency.

Methods: Idiopathic POI adolescents were categorized into two groups based on DHEAS and total testosterone (TT) measured by chemiluminescence. Low androgen group (LAG) was defined using cut-offs according to Tanner pubarche staging. Demographic, clinical, and laboratory data were compared. Morning cortisol <7 μg/dL and/or ACTH >96 or <5 pg/mL were planned to undergo ACTH stimulation testing, with a peak cortisol response <18 μg/dL considered insufficient.

Results: Forty-three adolescents, mean age 15.5 ± 1.3 years with a 46, XX karyotype, normal FMR1 mutation, FSH levels >40 mIU/mL, and low AMH levels were included. In 14 cases (37.8 %), DHEAS and TT were low. In the LAG, pubarche was absent in seven patients, and initial height SDS was significantly lower. Morning cortisol ranged from 7.9 to 23.5 μg/dL, with an ACTH of 29.4 ± 9.7 pg/mL. No differences in adrenal steroids or correlations between DHEAS and ACTH were observed.

Conclusions: Diminished androgen levels are prevalent in children with idiopathic POI. The potential for this condition to increase the risk of adrenal insufficiency and its impact on secondary ovarian insufficiency remains unclear. This study, the first of its kind in children, underscores the potential role of genetic factors in zona reticularis and ovarian development.

Objectives: Niemann-Pick type C (NPC) is a rare, autosomal recessive, neurodegenerative disorder caused by biallelic pathogenic variants in the NPC1 or NPC2 genes, leading to lysosomal lipid accumulation. NPC has an incidence of 1 in 100,000 live births and presents with a wide range of symptoms affecting visceral organs and the central nervous system. We aim to describe the diverse clinical presentations of NPC through case studies.

Case presentation: We report seven NPC patients from five families, showcasing the variability in clinical manifestations. The most common finding was hepatosplenomegaly (70 %), followed by prolonged jaundice (57 %) and neonatal cholestasis. Pulmonary alveolar proteinosis (PAP) was observed in three patients with biallelic pathogenic variants in the NPC2 gene. Neurological symptoms, including vertical gaze palsy and epilepsy, were noted in patients with juvenile onset form. Genetic analyses identified a novel homozygous c.315del (p.Thr106ProfsTer5) variant in the NPC2 gene, associated with early infantile onset.

Conclusions: NPC presents with diverse clinical findings across ages. Early hepatic symptoms in infants and neuropsychiatric issues in older patients warrant a high index of suspicion for NPC in such cases. A multidisciplinary approach is crucial for patient management, and further research is needed to clarify genotype-phenotype relationships in NPC.

Objectives: Phenylketonuria (PKU) and tyrosinemia type 3 (HT3) are both rare autosomal recessive disorders of phenylalanine-tyrosine metabolism. PKU is caused by a deficiency in phenylalanine hydroxylase (PAH), leading to elevated phenylalanine (Phe) and reduced tyrosine (Tyr) levels. HT3, the rarest form of tyrosinemia, is due to a deficiency in 4-hydroxyphenylpyruvate dioxygenase (HPD).

Case presentation: We report a 5-year-old girl diagnosed with both PKU and HT3. She presented with elevated Phe levels in neonatal screening, and subsequent biochemical tests revealed both hyperphenylalaninemia and elevated Tyr levels. Genetic analysis confirmed the diagnoses, identifying homozygous mutations in both the PAH and HPD genes. Dietary management to maintain optimal Phe and Tyr levels proved to be challenging due to the presence of these two coexisting pathologies especially during infections and due to dietary non-compliance, necessitating frequent adjustments in the treatment strategy.

Conclusions: This case highlights the importance of considering multiple metabolic disorders in patients with unexplained clinical and biochemical findings. Early diagnosis and stringent dietary management are crucial for preventing neurological damage and ensuring favorable outcomes in patients with concurrent metabolic disorders.

Objectives: Acrodermatitis dysmetabolica (AD) is a dermatologic manifestation associated with inherited metabolic disorders (IMDs), distinct from acrodermatitis enteropathica, which occurs solely due to zinc deficiency.

Case presentation: This report presents two pediatric cases: a 30-month-old girl with maple syrup urine disease (MSUD) experiencing AD secondary to severe isoleucine deficiency due to a protein-restricted diet, showing improvement with dietary adjustments, and a 2.5-month-old boy infant with propionic acidemia (PA) who developed AD alongside septic shock, which progressed despite intervention.

Conclusions: These cases emphasize the importance of identifying AD in IMDs and the critical need for meticulous monitoring of amino acid levels, as deficiencies may lead to severe complications.

Objectives: Surgery interventions for thyroid disorders are rare in pediatric population. This study aims to present our institution's 10-year experience regarding the surgical treatment and outcomes of thyroid pathologies in children and review the literature.

Methods: All pediatric patients who underwent thyroid surgery at our institution from April 2013 to October 2023 were retrospectively reviewed.

Results: The study included 57 patients with a median age of 15 years. 38 patients (66.6 %) were female, and 19 patients (33.3 %) were male. The most common indication for thyroid surgery was a nodule (71.9 %), followed by Graves' disease (10.5 %), multinodular goiter (8.7 %), and familial multiple endocrine neoplasia syndrome (8.7 %). Of the 57 patients, 36 (63.2 %) were diagnosed with thyroid neoplasia, with 28 (77.8 %) having papillary thyroid carcinoma (PTC), three (8.3 %) having medullary thyroid carcinoma (MTC), two (5.6 %) having follicular thyroid carcinoma (FTC). Temporary unilateral vocal cord paralysis and permanent unilateral vocal cord paralysis were seen in three patients (5.3 %) and in two patients (3.5 %) respectively. Persistent hypocalcemia and permanent hypoparathyroidism were noted in two patients (3.5 %), while transient hypocalcemia was observed in 13 patients (22.8 %). The presence of neoplasm did not appear to be associated with the incidence of hypocalcemia or vocal cord paralysis (p=0.115 and 0.652, respectively).

Conclusions: Thyroid pathologies in pediatric patients necessitate a multidisciplinary approach. Surgical management should be carefully evaluated in accordance with pediatric guidelines. Complication rate significantly decreases when surgery is performed by experienced surgeon.

Objectives: Subclinical hypothyroidism (SCH) is defined by elevated thyroid-stimulating hormone (TSH) levels (>5 mUI/L) and normal total and free thyroxine levels (fT4). There is ongoing debate over whether mild SCH should be treated. This study aims to assess the clinical course of normoponderal pediatric patients with SCH.

Methods: Retrospective study, involving normoponderal children and adolescents with SCH, followed at the Pediatrics Department of Hospital de Braga, from December 2007 to December 2022.

Results: We identified 47 children and adolescents with confirmed SCH. No sex predominance was found. The median age at diagnosis was 11 years. Most cases were idiopathic (59.6 %) and diagnosed during puberty (57.5 %). The majority (46.8 %) experienced spontaneous remission, while 38.3 % required levothyroxine (LT) therapy. Discharged patients were followed for a median of 25 months. No significant differences were seen in body mass index z-score, fT4 levels, heart rate, blood pressure, or lipid parameters. Significant differences were found in thyroid-stimulating hormone (TSH) levels and LT dosage. Thyroid peroxidase antibody (TPOAb) positivity was significantly correlated with SCH's natural history. Although initial TSH levels were not significantly associated with SCH's natural course, they predict treatment need. Individuals with initial TSH levels >6.47 mUI/L were more likely to require therapy. In the third year of follow-up, a significant strong negative correlation was found between TSH levels and high-density lipoprotein cholesterol.

Conclusions: SCH was self-limiting and benign in most cases. TPOAb positivity was a predictor of SCH's natural history, and the need for treatment was predicted by initial TSH levels.

Objectives: The aim of this study was to assess the impact of pre-operative imaging regarding selecting cases of children's who underwent laparoscopic adrenalectomy due to adrenal masses in two tertiary medical centers.

Methods: We performed a retrospective review of all laparoscopic adrenalectomy performed at two tertiary medical centers in Israel between 2017 and 2023.

Results: Sixteen (n=16) patients, 10 girls and six boys, underwent laparoscopic adrenalectomy through a transperitoneal approach. The median age was 10 years (range: eight months to 17.3 years). Six masses were incidentalomas. Preoperative imaging (ultrasonography, CT, and MRI) demonstrated a mass in the right adrenal (n=9) and left adrenal (n=7), with tumor sizes ranging from 1.8 to 5.3 cm in maximum diameter. Operative results showed minimal blood loss and no conversions to laparotomy. There were no postoperative complications. Pathological diagnoses included neuroblastoma (n=8), cortical hormone-secreting tumors (n=3), pheochromocytoma (n=2), adrenal cortical adenoma (n=2), and adrenal metastatic Ewing sarcoma (n=1). Eleven masses were defined as benign and five as malignant tumors.

Conclusions: Laparoscopic adrenalectomy appears to be a safe and effective technique in selected cases with adrenal masses. Among our cohort, malignant masses were more common compared to the predominantly benign adrenal masses seen in adults. Vascular encasement was a major factor in determining the feasibility of the laparoscopic approach, with preoperative imaging playing a critical role in this assessment.

Objectives: Auxology is essential for monitoring congenital adrenal hyperplasia (CAH). Data from prospective studies of newborn screening (NBS) are scarce.

Methods: Analysis of data extracted from a population-based prospective long-term follow-up survey study of children detected through NBS in Bavaria in 1999-2018. The study is based on standardized parent or patient questionnaires, supplemented by medical reports. Height, weight, and treatment data of 146 children/adolescents with classical CAH were analyzed. The entire observation period up to the age of 18 years was completed by 55 patients. Standard Deviation Scores (SDS) for height/body-mass-index (BMI) at different ages and the deviation of the height SDS at age 18 years from the parental target-height SDS were calculated.

Results: Male and female patients with CAH showed different and altered growth patterns, resulting in a median [IQR] SDS deviation from target height of -0.81 [-1.05, -0.41] in males and -0.35 [-0.90, 0.02] in females. BMI-SDS values were significantly (p<0.05) increased in males aged 6-16 years and in females aged 2 and 8-12 years. The average total steroid dose was higher in males (p<0.001). For deviations from target height, significant associations were found with sex (p<0.05) and adherence (p<0.01), but not with mutation group or steroid-dose. For BMI, none of the parameters showed a significant correlation.

Conclusions: Early treatment after NBS has helped to improve, but not to normalize, the development of height and weight in patients with CAH. Optimizing monitoring and treatment, preferably sex-specific, remains a challenge for clinical practice and research.