Quality of Life and Treatment Satisfaction in Participants with Maturity-Onset Diabetes of the Young: A Comparison to Other Major Forms of Diabetes.

Aims: We investigated the quality of life (QoL), treatment satisfaction and perception of genetic results in participants with Maturity-Onset Diabetes of the Young (MODY) and compared the results with those of subjects with type 1 (T1D) or type 2 (T2D) diabetes.

Methods: A total of 162 adults with GCK-MODY, 62 with HNF1A-MODY and 29 with HNF4A-MODY answered the questionnaire Audit of Diabetes Dependent Quality of Life, the Diabetes Treatment Satisfaction Questionnaire and non-validated instrument examining the respondent's perception of the genetic results. Data from GCK-MODY patients were compared with 84 participants with T2D and HNF-MODY subjects were compared with 81 participants having T1D.

Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study.

Background: Disordered thyroid hormone transport, due to mutations in the SLC16A2 gene encoding monocarboxylate transporter 8 (MCT8), is characterised by intellectual and motor disability resulting from cerebral hypothyroidism and chronic peripheral thyrotoxicosis. We sought to systematically assess the phenotypic characteristics and natural history of patients with MCT8 deficiency.

Methods: We did an international, multicentre, cohort study, analysing retrospective data from Jan 1, 2003, to Dec 31, 2019, from patients with MCT8 deficiency followed up in 47 hospitals in 22 countries globally.

Congenital Hyperinsulinism Caused by Novel Homozygous KATP Channel Gene Variants May Be Linked to Unexplained Neonatal Deaths among Kurdish Consanguineous Families.

Introduction: Neonatal hypoglycemia due to congenital hyperinsulinism (CHI) is a potentially life-threatening condition. Biallelic pathogenic variants in KATP channel subunit genes (ABCC8, KCNJ11), causing severe forms of CHI, are more prevalent in regions with a significant rate of consanguinity and may lead to unexplained neonatal deaths. We hypothesized that KATP channel gene variants are the cause of CHI in three unrelated children from consanguineous Kurdish families with histories of four unexplained neonatal deaths with convulsions.

Effectiveness and safety of the tri-iodothyronine analogue Triac in children and adults with MCT8 deficiency: an international, single-arm, open-label, phase 2 trial.

Background: Deficiency of the thyroid hormone transporter monocarboxylate transporter 8 (MCT8) causes severe intellectual and motor disability and high serum tri-iodothyronine (T) concentrations (Allan-Herndon-Dudley syndrome). This chronic thyrotoxicosis leads to progressive deterioration in bodyweight, tachycardia, and muscle wasting, predisposing affected individuals to substantial morbidity and mortality. Treatment that safely alleviates peripheral thyrotoxicosis and reverses cerebral hypothyroidism is not yet available.

Could a combination of heterozygous ABCC8 and KCNJ11 mutations cause congenital hyperinsulinism?

Background: Congenital hyperinsulinism (CHI) is frequently caused by mutations in one of the KATP channel subunits encoded by the genes ABCC8 and KCNJ11. The effect of simultaneous mutations in both of these genes on the pancreatic β-cell function is not known and patients with CHI carrying both ABCC8 and KCNJ11 mutations have not yet been reported. We questioned if a combination of heterozygous mutations in the ABCC8 and KCNJ11 genes could also lead to β-cell dysfunction presenting as CHI.

[Congenital hyperinsulinism: Loss of B-cell self-control].

Congenital hyperinsulinism is a serious blood glucose regulation defect that interferes with brain development, leading to mental retardation, neurological sequelae and secondary epilepsy and ultimately may be life-threatening. Congenital hyperinsulinism (CHI) is caused by genetic defects of regulation of insulin secretion that induce insulin oversecretion in intrauterine life and postnatally. The clinical consequence is fetal macrosomia and subsequently neonatal and infantile hypoglycaemia.

Severe Hyperinsulinaemic Hypoglycaemia in Beckwith-Wiedemann Syndrome due to Paternal Uniparental Disomy of 11p15.5 Managed with Sirolimus Therapy.

Background: Almost half of the children with Beckwith-Wiedemann syndrome (BWS) will develop hyperinsulinaemic hypoglycaemia (HH). In the majority of BWS cases, HH will be transient; however, approximately in 5% of them, HH will be severe and often medically-unresponsive. Children with BWS due to paternal uniparental disomy (UPD) of chromosome 11p15 belong to this severe category and have traditionally required near-total pancreatectomy.

High Incidence of Heterozygous ABCC8 and HNF1A Mutations in Czech Patients With Congenital Hyperinsulinism.

Context: Congenital hyperinsulinism of infancy (CHI) represents a group of heterogeneous disorders characterized by oversecretion of insulin from pancreatic β-cells causing severe hypoglycemia.

Objective: We studied the distribution of genetic causes of CHI in a Czech population.

Methods: Countrywide collection of patients with CHI included 40 subjects (12 females, median age of diagnosis, 1 wk [interquartile range, 1-612 wk]).

The Diagnosis and Management of Hyperinsulinaemic Hypoglycaemia.

Insulin secretion from pancreatic β-cells is tightly regulated to keep fasting blood glucose concentrations within the normal range (3.5-5.5 mmol/L).