Beckwith-Wiedemann syndrome (BWS) is a rare genomic imprinting disorder that affects multiple systems. Major features can manifest as large birth weight, anterior abdominal wall defects, macroglossia, hyperinsulinism, organomegaly hemihypertrophy, and renal abnormalities. Characteristic facies manifested as midface hypoplasia, infraorbital creases, facial nevus simplex, and anterior linear ear lobe creases/posterior helical ear pits, with a predisposition to tumor development. This case report describes a Saudi infant born at 38+5 weeks gestation via elective cesarean section to a 33-year-old G3P2+0 mother, with a family history of type 1 diabetes and Down syndrome. Prenatal ultrasound revealed an anterior abdominal wall defect. Postnatally, the infant exhibited macrosomia, macroglossia, and omphalocele. Genetic testing confirmed paternal disomy of the imprinted region in 11p15.5. The infant underwent successful omphalocele repair but experienced respiratory distress, and seizures on the third day of life. Intubation, ventilation, and antiepileptic treatment were initiated. Subsequent investigations revealed right upper lobe collapse, neonatal seizures on electroencephalogram (EEG), and thin corpus callosum on magnetic resonance imaging (MRI). Feeding difficulties led to elective partial glossectomy at two months of age. During her hospital stay two days post surgery, the infant developed persistent hypoglycemia requiring high glucose infusion rates. Extensive endocrine evaluation revealed high insulin and cortisol levels. Subcutaneous octreotide was administered with minimal response. After 15 days of careful glucose tapering, the infant\'s blood glucose stabilized, reaching feeding targets. The patient was discharged with follow-up appointments. This comprehensive case highlights the complexity of managing severe relapsing hypoglycemia in an infant with BWS.

The best-known etiologies of hyperinsulinemic hypoglycemia are insulinoma, non-insulinoma pancreatogenous hypoglycemic syndrome, autoimmune processes, and factitious hypoglycemia. In 2009, a disease not associated with classic genetic syndromes and characterized by the presence of multiple pancreatic lesions was described and named insulinomatosis. We present the clinical and pathologic features of four patients with the diagnosis of insulinomatosis, aggregated new clinical data, reviewed extensively the literature, and illustrated the nature and evolution of this recently recognized disease. One of our patients had isolated (without fasting hypoglycemia) postprandial hypoglycemia, an occurrence not previously reported in the literature. Furthermore, we reported the second case presenting malignant disease. All of them had persistent/recurrent hypoglycemia after the first surgery even with pathology confirming the presence of a positive insulin neuroendocrine tumor. In the literature review, 27 sporadic insulinomatosis cases were compiled. All of them had episodes of fasting hypoglycemia except one of our patients. Only two patients had malignant disease, and one of them was from our series. The suspicion of insulinomatosis can be raised before surgery in patients without genetic syndromes, with multiple tumors in the topographic investigation and in those who had persistent or recurrent hypoglycemia after surgical removal of one or more tumors. The definitive diagnosis is established by histology and immunohistochemistry and requires examination of the \"macroscopically normal pancreas.\" Our case series reinforces the marked predominance in women, the high frequency of recurrent hypoglycemia, and consequently, a definitive poor response to the usual surgical treatment.

Differential diagnosis of hypoglycemia in the non-diabetic adult patient is complex and comprises various diseases, including endogenous hyperinsulinism caused by functional β-cell disorders. The latter is also designated as nesidioblastosis or non-insulinoma pancreatogenous hypoglycemia syndrome (NIPHS). Clinically, this rare disease presents with unspecific adrenergic and neuroglycopenic symptoms and is, therefore, often overlooked. A combination of careful clinical assessment, oral glucose tolerance testing, 72 h fasting, sectional and functional imaging, and invasive insulin measurements can lead to the correct diagnosis. Due to a lack of a pathophysiological understanding of the condition, conservative treatment options are limited and mostly ineffective. Therefore, nearly all patients currently undergo surgical resection of parts or the entire pancreas. Consequently, apart from faster diagnosis, more elaborate and less invasive treatment options are needed to relieve the patients from the dangerous and devastating symptoms. Based on a case of a 23-year-old man presenting with this disease in our department, we performed an extensive review of the medical literature dealing with this condition and herein presented a comprehensive discussion of this interesting disease, including all aspects from epidemiology to therapy.

Insulinomas are very rare in childhood with sparse knowledge on the clinical aspects and the presence of Multiple Endocrine Neoplasia type 1 (MEN1).
We conducted a retrospective review of patients diagnosed with insulinoma between 1995 and 2021, presenting to one referral centre in Russia. Clinical, biochemical, genetic, imaging and histological data were collected. In addition, follow-up and family data were obtained.
A total of twenty-two children aged 5 to 16 years were identified. The median (range) gap between the first hypoglycaemia symptoms and diagnosis was 10 (1-46) months. Twelve children (55%) were misdiagnosed to have epilepsy and were treated with anticonvulsants before hypoglycemia was revealed. Contrast enhanced MRI and/or CT were accurate to localize the lesion in 82% (n=18). Five patients (23%) had multiple pancreatic lesions. All children underwent surgical treatment. The median (range) diameter of removed tumors was 1.5 (0.3-6) cm. Histopathological studies confirmed the presence of insulinoma in all cases. Immunohistochemical studies revealed G2 differentiation grade in 10 out of 17 cases. Two patients were diagnosed with metastatic insulinoma. One of them had metastases at the time of insulinoma diagnosis, while the other was diagnosed with liver metastases eight years after the surgery. Eight children (36%) were found to carry MEN1 mutations, inherited n=5, de novo n=1, no data, n=2. Children with MEN1 had significantly higher number of pancreatic tumors compared to sporadic cases. All of them developed additional MEN1 symptoms during the following 2-13 years. In the five patients with inherited MEN1, seven family members had hitherto undiscovered MEN1 manifestations.
In this large cohort of children with rare pediatric insulinomas, MEN1 syndrome and G2 tumors were frequent, as well as hitherto undiscovered MEN1 manifestations in family members. Our data emphasize the need of genetic testing in all children with insulinoma and their relatives, even in the absence of any other features, as well as the importance of a prolonged follow-up observation.

Hypoglycemia may present with a multitude of signs and symptoms ranging from subjective feelings of anxiety or diaphoresis to neuroglycopenic manifestations of altered sensorium or seizure. The differential diagnosis of hypoglycemic disorders is broad, and in rare instances may occur following intentional induction by undisclosed insulin administration or insulin secretagogue ingestion in patients with an underlying factitious disorder. While basic laboratory studies can reliably confirm the presence of exogenous insulin in patients with hyperinsulinemic hypoglycemia, increased endogenous insulin secretion following sulfonylurea ingestion can mimic a biochemical pattern of findings also seen with insulinoma, a rare pancreatic insulin-producing tumor. We present a case of severe hypoglycemia manifesting as diminished consciousness in a patient with multiple medical comorbidities. Following initial laboratory workup suggestive of endogenous hyperinsulinemic hypoglycemia, the results of a serum oral hypoglycemic panel confirmed the presence of glipizide, an unprescribed insulin secretagogue of the sulfonylurea class, in the patient\'s serum. In conjunction with psychiatric services, the patient was diagnosed with an underlying factitious disorder and her hypoglycemia was deemed likely the result of surreptitious sulfonylurea ingestion as a pathologic healthcare-seeking behavior. Our case report and subsequent review shed light on critical components in the diagnostic approach to hypoglycemic disorders, which carry significant morbidity for patients regardless of the underlying cause and emphasize several clinical and ethical considerations associated with the identification and management of persons with factitious disorder in medical practice.

The KCNJ11 gene encodes the Kir6.2 subunit of the adenosine triphosphate-sensitive potassium (KATP ) channel, which plays a key role in insulin secretion. Monogenic diseases caused by KCNJ11 gene mutation are rare and easily misdiagnosed. It has been shown that mutations in the KCNJ11 gene are associated with neonatal diabetes mellitus (NDM), maturity-onset diabetes of the young 13 (MODY13), type 2 diabetes mellitus (T2DM), and hyperinsulinemic hypoglycemia. We report four patients with KCNJ11 gene mutations and provide a systematic review of the literature. A boy with diabetes onset at the age of 1 month was misdiagnosed as type 1 diabetes mellitus (T1DM) for 12 years and received insulin therapy continuously, resulting in poor glycemic control. He was diagnosed as NDM with KCNJ11 E322K gene mutation, and glibenclamide was given to replace exogenous insulin. The successful transfer time was 4 months, much longer than the previous unsuccessful standard of 4 weeks. The other three patients were two sisters and their mother; the younger sister was misdiagnosed with T1DM at 13 years old, while the elder sister was diagnosed with diabetes (type undefined) at 16 years old. They were treated with insulin for 3 years, with poor glycemic control. Their mother was diagnosed with T2DM and achieved good glycemia control with glimepiride. They were diagnosed as MODY13 because of the autosomal dominant inheritance of two generations, early onset of diabetes before 25 years of age in the two sisters, and the presence of the KCNJ11 N48D gene mutation. All patients successfully transferred to sulfonylureas with excellent glycemic control. Therefore, the wide spectrum of clinical phenotypes of glucose dysmetabolism caused by KCNJ11 should be recognized to reduce misdiagnosis and implement appropriate treatment.
KCNJ11基因编码胰岛β细胞上ATP敏感性钾通道( KATP )的Kir6.2亚基, 是调节胰岛素分泌的重要基因。KCNJ11基因突变引起的单基因疾病较罕见, 在临床工作中容易误诊。研究表明, KCNJ11基因突变不仅可导致新生儿糖尿病(NDM), 还与青少年发病的成人糖尿病13(MODY13)、2型糖尿病(T2DM)、婴儿持续性高胰岛素血症性低血糖症(PHHI)的发生有关。本文报告了4例KCNJ11基因突变的患者并对文献进行系统回顾。 病例1是1例病程长达12年, 长期误诊为1型糖尿病(T1DM)而接受胰岛素治疗, 但血糖控制不佳、频发低血糖的糖尿病患者。询问病史发现患者为出生后1月龄起病, 行基因检测明确为KCNJ11 E322K基因突变。诊断为NDM, 予以格列本脲成功有效地替代外源性胰岛素治疗, 但转换成功的时间长达4个月, 远长于目前国际所报道的不成功标准4周。其他三例患者为一个家系, 包括两姐妹及其母亲, 先证者为家系中的妹妹, 她在13岁时被诊为T1DM, 同时姐姐在16岁时发现血糖升高, 被诊断为糖尿病(分型待定)。两姐妹使用胰岛素治疗3年, 血糖控制不佳。她们的母亲在36岁时诊断为T2DM, 口服格列美脲取得良好血糖控制。该家系有两代直系亲属患有糖尿病, 且符合常染色体显性遗传规律; 两姐妹均在25岁以前诊断糖尿病, 行基因检测明确存在KCNJ11 N48D基因突变。因此被诊断为MODY13。使用格列本脲治疗后, 两姐妹成功脱离胰岛素治疗, 且血糖控制理想。 以上病例提示我们应认识到临床上存在KCNJ11基因突变所致不同类型和不同程度的糖代谢异常, 我们需要根据患者疾病特征及时发现, 减少误诊并予以合理的精准治疗。.

BACKGROUND: The p.R63W mutation in hepatocyte nuclear factor-4 alpha (HNF4A) leads to a heterogeneous group of disorders with various clinical presentations. Recently, patients with congenital hyperinsulinism and Fanconi syndrome due to the p.R63W mutation in HNF4A have been described. Although other clinical variations such as liver dysfunction have been associated with HNF4A mutations, hearing impairment has not previously been associated. We report the case of a patient with Fanconi syndrome and hyperinsulinemic hypoglycemia caused by the mutation of HNF4A presenting with additional auditory phenotypes.
METHODS: We present a case report of a 10-year-old girl of Chinese Han ethnicity who presented with renal Fanconi syndrome, infantile hyperinsulinemic hypoglycemia, and transient cholestasis. In addition, she presented with bilateral severe hearing loss. Gene analysis showed a heterozygous p.R63W mutation in the HNF4A gene that is responsible for Fanconi syndrome and hyperinsulinemic hypoglycemia.
CONCLUSIONS: This is the first case of HNF4A mutation associated with an auditory phenotype. It expands the clinical phenotypes and supports speculation in the literature that HNF4A may be a candidate gene for deafness. In conclusion, hearing loss may be found in children with HNF4A-related Fanconi syndrome, and auditory function should be assessed.