Journal of Pediatric Endocrinology & Metabolism最新文献

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.

Materials and 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 mcg/dL and/or ACTH >96 or <5 pg/mL were planned to undergo ACTH stimulation testing, with a peak cortisol response <18 mcg/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 mcg/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 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 authors sought to assess whether the age of 18 reflects a true pathological inflection point that justifies transitioning between pediatric and adult paradigms of care with differentiated thyroid cancer (DTC).

Methods: A retrospective chart review was conducted for patients aged 12-24 undergoing hemithyroidectomy or total thyroidectomy for papillary or follicular thyroid carcinoma from 2010 to 2020.

Results: A total of 153 patients receiving surgery for DTC were assessed for pathological stage, nodal metastasis, and thyroid neoplasm characteristics. When comparing pathologic tumor staging of patients <18 vs. ≥18 years old, there was a significant relationship between age and pT stage (p=0.009), but not between age and pN stage (p=0.319). However, when comparing patients ≤15 vs. >15 years, there was a significant relationship between age and pT stage (p=0.015) and age and pN stage (p=0.016). Patients ≤15 years of age most commonly had stage pT2 tumors (48.9 %, n=22), whereas most >15 years had stage pT1 tumors (37.9 %, n=41). Of patients whose lymph nodes were analyzed, patients ≤15 years were most likely to have pN1b disease (31.1 %, n=14), while patients >15 years were most likely to have pN0 disease (33.3 %, n=36).

Conclusions: In this sample, separating children and adults at an age of 15, rather than 18, yielded more significant differences in risk of nodal involvement. Markers of invasive histology were more common in patients older than 15, while nodal involvement was more common in patients 15 and under.

Objectives: Graves' disease is the leading cause of hyperthyroidism in children. Only a small percentage of pediatric patients achieve remission with anti-thyroid drug treatment (ATD), and both definitive therapies (thyroidectomy, or radioiodine thyroid ablation) cause lifelong hypothyroidism. Our objective was to evaluate the outcome of patients with pediatric Graves' disease (PGD), treated at a single tertiary center, focusing on response to medical treatment, remission rate, adverse reactions (AR), definitive treatment (DT), and potential predictive factors for remission.

Methods: Data from clinical charts of 130 patients diagnosed with PGD between 2006 and 2021 were collected: epidemiological, clinical, biochemical characteristics, outcome, remission, adverse reactions (AR), and DT were registered. Predictive factors at diagnosis were evaluated for 88 patients diagnosed at our center.

Results: Our patients were 78 % female, 98 % Hispanic, with a median age of 12.7 years (range 1.7-17.3 years). Fourteen (11 %) had Down syndrome. Severe thyrotoxicosis (FT4>5.5 ng/dL) was seen at diagnosis in 66 %. Initially, 129/130 received ATD; during the study, 17 participants (13 %) reached remission, with a median ATD duration of 3.1 years (range 1.3-6.1 years). The chance of remaining hyperthyroid was 65 %. Only one patient relapsed 1.3 years post-ATD. Forty-six percent (59/129) needed DT, 31 % (40/129) were lost to follow-up, and 10 % (11/129) remained on ATD. AR affected 26 % of the patients and most (74 %) occurred within the first 3 months, half of them severe enough to discontinue ATD. No significant predictive factors were identified.

Results: ATD, our first-line treatment, resulted in low remission rates for Hispanic pediatric patients with severe thyrotoxicosis at diagnosis. Poor adherence issues contributed to the indication of DT (46 %) and loss to follow-up (31 %) during the studied period. Based on our findings, DT should be considered at 4 years of ATD in persisting PGD.

Conclusions: ATD, our first line treatment, resulted in low remission rates for Hispanic pediatric patients with severe thyrotoxicosis at diagnosis. Poor adherence issues contributed to the indication of DT (46 %) and loss to follow-up (31 %) during the studied period. Based on our findings, DT should be considered at 4 years of ATD in persisting PGD.

Objectives: Sialidosis type 1 is a rare autosomal recessive lysosomal storage disorder caused by pathogenic variants in the NEU1 gene, which encodes the sialic acid-degrading enzyme α-neuraminidase. Sialidosis type 1 is a milder form with a late-onset phenotype, characterized by progressive myoclonic epilepsy and ataxia with cherry-red spots. Sialidosis type 2 is an early-onset and more severe form presenting with dysmorphic features, hepatosplenomegaly and cognitive delay. Clinical diagnosis is usually supported by increased urinary bound sialic acid excretion and confirmed by genetic analysis or demonstration of α-neuraminidase enzyme deficiency in cultured fibroblasts. The aim of this study was to present a case of type 1 sialidosis, review the literature, and investigate genotype-phenotype correlations, symptom frequencies, and race-specific mutations in patients diagnosed with type 1 sialidosis.

Case presentation: We report herein a family of four Turkish siblings affected with sialidosis type 1 associated with a homozygous variant, c.403G>A p. (Asp135Asn), in the NEU1 gene. A systematic literature review on sialidosis type 1 was carried out, by the PubMed database was searched using keywords included sialidosis and/or NEU1 gene. We selected case reports or series that included genetically confirmed type 1 sialidosis from 1996 to 2023. So far, nearly genetically confirmed 80 patients from unrelated 65 families, more than 40 NEU1 disease causing mutations, have been identified in patients with sialidosis type 1. Among the reported mutations, missense variants are the most common, and few nonsense, frameshift, exonic duplications or small deletions have been reported. c.239C>T p. (Pro80Leu) variant in Chinese and Japanese patients, c.649G>A p. (Val217Met) variant in Japanese patients, c.880C>T p. (Arg294Cys) variant in Indian patients, c.629C>T p. (Pro210Leu) variant in Ecuadorian patients, c.982G>A p. (Gly328Ser) variant in Italian patients, and c.403G>A p (Asp135Asn) and c.625del p. (Glu209Serfs*94) variants in Turkish patients were found higher.

Conclusions: Race-specific variants were found with higher percentages in certain populations.