Familial and early recurrent pheochromocytoma in a child with a novel in-frame duplication variant of .

Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors often linked to underlying genetic variants. Genetic analysis can promote gene-adjusted, specific follow-up, and surveillance protocols for both patients and their families at risk. We report the case of a 7-yr-old boy with bilateral pheochromocytoma, which recurred a year after partial adrenalectomy.

RMRP-related short stature: A report of six additional Japanese individuals with cartilage hair hypoplasia and literature review.

Biallelic pathogenic variants in RMRP, the gene encoding the RNA component of RNase mitochondrial RNA processing enzyme complex, have been reported in individuals with cartilage hair hypoplasia (CHH). CHH is prevalent in Finnish and Amish populations due to a founder pathogenic variant, n.71A > G.

A MinION-based Long-Read Sequencing Application With One-Step PCR for the Genetic Diagnosis of 21-Hydroxylase Deficiency.

Context: Recently developed long-read sequencing (LRS) technology has been considered an option for CYP21A2 analysis. However, the clinical use of LRS for CYP21A2 analysis is limited.

Objective: This study's objective is to develop an efficient and low-cost LRS system for CYP21A2 screening.

BMP2 is a potential causative gene for isolated dextrocardia situs solitus.

BMP2 (bone morphogenic protein-2) is a member of the TGF-β superfamily and has essential roles in the development of multiple organs, including osteogenesis. Because of its crucial role in organ and skeletal development, Bmp2 null mice is fetal lethal. The recent report has characterized multiple patients with BMP2 haploinsufficiency, describing individuals with BMP2 sequence variants and deletions associated with short stature without endocrinological abnormalities, a recognizable craniofacial gestalt, skeletal anomalies, and congenital heart disease.

Growth Hormone Injection Log Analysis with Electronic Injection Device for Qualifying Adherence to Low-Irritant Formulation and Exploring Influential Factors on Adherence.

Introduction: Although the treatment success of long-term growth hormone therapy (GHT) is dependent on maintaining patients' adherence to treatment, marked variations in adherence levels among children with GHT (eg, 7-71% nonadherence) have been reported. Barriers to or promoters of GHT adherence have been discussed and investigated, and digital health technologies, such as electronic GH injection devices, may have the potential to assess adherence to GHT more accurately. Thus, we conducted a multicenter, retrospective cohort study using GH injection log analysis of an electronic GH device, GROWJECTORL, to qualify adherence and explore the factors influencing adherence.

Phenotypic Variation in 46,XX Disorders of Sex Development due to the Fourth Zinc Finger Domain Variant of WT1: A Familial Case Report.

Introduction: The variants in the zinc finger (ZF) domains 1-3 in WT1 are one of the major causes of 46,XY disorders of sex development (DSD). Recently, variants in the fourth ZF (ZF4 variants) were reported to cause 46,XX DSD. However, all the 9 patients reported were de novo, and no familial cases were identified.

A novel variant of NR5A1, p.R350W implicates potential interactions with unknown co-factors or ligands.

Introduction: NR5A1 and NR5A2 belong to an orphan nuclear receptor group, and approximately 60% of their amino acid sequences are conserved. Transcriptional regulation of NR5A receptors depends on interactions with co-factors or unidentified ligands.

Purpose And Methods: We employed in vitro and in silico analysis for elucidating the pathophysiology of a novel variant in the ligand-binding domain of NR5A1, p.

Clinical report: Chronic liver dysfunction in an individual with an AMOTL1 variant.

AMOTL1 is a member of the Motin protein family and localizes to tight junctions and is involved in cell polarity and paracellular permeability. Pathological variants have been reported in three patients from two separate families in recent years. The clinical spectrum includes cleft lip and palate along with a high incidence of congenital cardiac disease and ear malformations.

The High Relevance of 21-Deoxycortisol, (Androstenedione + 17α-Hydroxyprogesterone)/Cortisol, and 11-Deoxycortisol/17α-Hydroxyprogesterone for Newborn Screening of 21-Hydroxylase Deficiency.

Context: There are limited reports on the detailed examination of steroid profiles for setting algorithms for 21-hydroxylase deficiency (21OHD) screening by liquid chromatography-tandem mass spectrometry (LC-MS/MS).

Objective: We aimed to define an algorithm for newborn screening of 21OHD by LC-MS/MS, measuring a total of 2077 dried blood spot samples in Tokyo.

Methods: Five steroids (17α-hydroxyprogesterone [17αOHP], 21-deoxycortisol [21DOF], 11-deoxycortisol [11DOF], androstenedione [4AD], and cortisol [F]) were included in the panel of LC-MS/MS.

Clinical guidelines for the diagnosis and treatment of 21-hydroxylase deficiency (2021 revision).

Congenital adrenal hyperplasia is a category of disorders characterized by impaired adrenocortical steroidogenesis. The most frequent disorder of congenital adrenal hyperplasia is 21-hydroxylase deficiency, which is caused by pathogenic variants of and is prevalent between 1 in 18,000 and 20,000 in Japan. The clinical guidelines for 21-hydroxylase deficiency in Japan have been revised twice since a diagnostic handbook in Japan was published in 1989.

Atrophic autoimmune thyroiditis complicated with systemic lupus erythematosus.

Atrophic autoimmune thyroiditis (AAT) is a type of autoimmune thyroiditis that causes hypothyroidism without thyroid enlargement. AAT is distinguished from Hashimoto's disease (HD) by the absence of thyroid enlargement. AAT is rare in children and clinically characterised by severe primary hypothyroidism.

Toward Improving the Transition of Patients With Congenital Adrenal Hyperplasia From Pediatrics to Adult Healthcare in Japan.

The transition of patients with childhood-onset chronic diseases from pediatric to adult healthcare systems has recently received significant attention. Since 2013, the Japan Pediatric Society developed working groups to formulate guidelines for transition of patients with childhood-onset chronic diseases from pediatric to their disease specialty. Herein, we report on the activities of the Japan Society of Pediatric Endocrinology (JSPE) and the current status of transition medicine for 21-hydroxylase deficiency (21-OHD) in Japan.

Two ovarian candidate enhancers, identified by time series enhancer RNA analyses, harbor rare genetic variations identified in ovarian insufficiency.

The genetic regulation of ovarian development remains largely unclear. Indeed, in most cases of impaired ovarian development-such as 46,XX disorders of sex development (DSD) without SRY, and premature ovarian insufficiency (POI)-the genetic causes have not been identified, and the vast majority of disease-associated sequence variants could lie within non-coding regulatory sequences. In this study, we aimed to identify enhancers of five ovarian genes known to play key roles in early ovarian development, basing our analysis on the expression of enhancer derived transcripts (eRNAs), which are considered to characterize active enhancers.

Infliximab treatment for refractory COVID-19-associated multisystem inflammatory syndrome in a Japanese child.

Patients with multisystem inflammatory syndrome in children (MIS-C) can develop clinical features resembling Kawasaki disease (KD). A full picture of MIS-C in East Asia which has higher incidence of KD than other regions remains unclear. We report on a 15-year-old Japanese boy with refractory MIS-C who was successfully treated with infliximab.

Endocrinopathies in Inborn Errors of Immunity.

Inborn errors of immunity (IEI), caused by hereditary or genetic defects, are a group of more than 400 disorders, in which the immune system, including lymphocytes, neutrophils, macrophages, and complements, does not function properly. The endocrine system is frequently affected by IEI as an associated clinical feature and a complex network of glands which regulate many important body functions, including growth, reproduction, homeostasis, and energy regulation. Most endocrine disorders associated with IEI are hypofunction which would be treated with supplementation therapy, and early diagnosis and appropriate management are essential for favorable long-term outcomes in patients with IEI.

Adrenal suppression and anthropometric data at two years of age was not influenced by the initial hydrocortisone dose in patients with 21-hydroxylase deficiency.

In contrast to the glucocorticoid maintenance therapy employed in patients with 21 hydroxylase deficiency (21OHD), the initial therapy remains to be optimized. The Japanese Society for Pediatric Endocrinology recommends a hydrocortisone (HC) dose of 25-100 mg/m, which is higher than that employed in Western countries. Herein, we aimed to retrospectively verify the impact of initial HC treatment during infancy and early childhood.

Central diabetes insipidus developing in a 6-year-old patient 4 years after the remission of unifocal bone Langerhans cell histiocytosis.

A six-year-old boy was referred with a one-and-a-half months history of polyuria and polydipsia. At the age of two, he had a single lytic bone lesion in his femoral head, diagnosed as Langerhans cell histiocytosis (LCH) by biopsy at another hospital. As no other affected organs were detected and the affected bone lesion was self-limited, he was not followed up afterward and was doing well.

Marked clinical heterogeneity in congenital hyperinsulinism due to a novel homozygous ABCC8 mutation.

Background: The most severe forms of congenital hyperinsulinism (CHI) are caused by inactivating mutations of two KATP channel genes, KCNJ11 and ABCC8. Unresponsiveness to diazoxide and need for subtotal pancreatectomy can usually be predicted by genetic form, particularly biallelic mutations in KATP channel genes. A few reports indicated marked clinical heterogeneity in siblings with identical biallelic mutations in ABCC8.