Availability and Access to Medications for Puberty Induction and Maintenance in Adolescents with Hypogonadism in the Arab Region.

Background: Inducing puberty in hypogonadal patients enables achieving normal final adult height and healthy bone mass accrual and improves fertility potential. Reliable availability and access to medicines remain a challenge around the world, particularly in low-income countries. Aim: We aimed to describe the availability/access to medications used for inducing and maintaining puberty in centers within the Arab region. Method: A cross-sectional survey was conducted using a link to an online questionnaire, which was emailed to paediatric endocrinologists in the Arab region. The questionnaire consisted of three questions related to the availability of various forms of sex hormones. Results: 99 physicians from 16 countries participated in the study. The commonest available form of estrogen was conjugated estrogen (29% of centers), followed by ethinylestradiol (26%). Depot estradiol was available in 11 centers, while topical estrogen preparations of gel and patches were available in 6 and 10 centers, respectively. Medroxy progesterone was available in 26% of the centers, followed by norethisterone (24%). The combined forms of oral and transdermal patches of estrogen/progesterone were available in 35% and 9% of centers, respectively. Intramuscular testosterone (Sustanon) was the most commonly available preparation of testosterone, followed by the depot injection (Nebido), oral testosterone, and testosterone gel and cream. Conclusions: We report the first available data on medications used for puberty induction and maintenance in paediatric hypogonadism in the Arab region. Recommended preparations for this purpose are not widely available. Creating an essential list of medications used in paediatric endocrinology disorders might improve availability, access, and consequently practice.

Expanding the Clinical Spectrum Associated With GLIS3 Mutations.

CONTEXT: GLIS3 (GLI-similar 3) is a member of the GLI-similar zinc finger protein family encoding for a nuclear protein with 5 C2H2-type zinc finger domains. The protein is expressed early in embryogenesis and plays a critical role as both a repressor and activator of transcription. Human GLIS3 mutations are extremely rare. OBJECTIVE: The purpose of this article was determine the phenotypic presentation of 12 patients with a variety of GLIS3 mutations. METHODS: GLIS3 gene mutations were sought by PCR amplification and sequence analysis of exons 1 to 11. Clinical information was provided by the referring clinicians and subsequently using a questionnaire circulated to gain further information. RESULTS: We report the first case of a patient with a compound heterozygous mutation in GLIS3 who did not present with congenital hypothyroidism. All patients presented with neonatal diabetes with a range of insulin sensitivities. Thyroid disease varied among patients. Hepatic and renal disease was common with liver dysfunction ranging from hepatitis to cirrhosis; cystic dysplasia was the most common renal manifestation. We describe new presenting features in patients with GLIS3 mutations, including craniosynostosis, hiatus hernia, atrial septal defect, splenic cyst, and choanal atresia and confirm further cases with sensorineural deafness and exocrine pancreatic insufficiency. CONCLUSION: We report new findings within the GLIS3 phenotype, further extending the spectrum of abnormalities associated with GLIS3 mutations and providing novel insights into the role of GLIS3 in human physiological development. All but 2 of the patients within our cohort are still alive, and we describe the first patient to live to adulthood with a GLIS3 mutation, suggesting that even patients with a severe GLIS3 phenotype may have a longer life expectancy than originally described.

SLC2A2 mutations can cause neonatal diabetes, suggesting GLUT2 may have a role in human insulin secretion.

AIMS: The gene SLC2A2 encodes GLUT2, which is found predominantly in pancreas, liver, kidney and intestine. In mice, GLUT2 is the major glucose transporter into pancreatic beta cells, and biallelic Slc2a2 inactivation causes lethal neonatal diabetes. The role of GLUT2 in human beta cells is controversial, and biallelic SLC2A2 mutations cause Fanconi-Bickel syndrome (FBS), with diabetes rarely reported. We investigated the potential role of GLUT2 in the neonatal period by testing whether SLC2A2 mutations can present with neonatal diabetes before the clinical features of FBS appear. METHODS: We studied SLC2A2 in patients with transient neonatal diabetes mellitus (TNDM; n = 25) or permanent neonatal diabetes mellitus (PNDM; n = 79) in whom we had excluded the common genetic causes of neonatal diabetes, using a combined approach of sequencing and homozygosity mapping. RESULTS: Of 104 patients, five (5%) were found to have homozygous SLC2A2 mutations, including four novel mutations (S203R, M376R, c.963+1G>A, F114LfsX16). Four out of five patients with SLC2A2 mutations presented with isolated diabetes and later developed features of FBS. Four out of five patients had TNDM (16% of our TNDM cohort of unknown aetiology). One patient with PNDM remains on insulin at 28 months. CONCLUSIONS: SLC2A2 mutations are an autosomal recessive cause of neonatal diabetes that should be considered in consanguineous families or those with TNDM, after excluding common causes, even in the absence of features of FBS. The finding that patients with homozygous SLC2A2 mutations can have neonatal diabetes supports a role for GLUT2 in the human beta cell.