A retrospective analysis of congenital anomalies in congenital hypothyroidism.

Objectives We evaluated the spectrum of diseases accompanying congenital hypothyroidism (CH) in the United Arab Emirates and compared them with internationally studied patterns. Methods The presented retrospective cross-sectional study took place in two government tertiary care centres. In total, 204 patients with a confirmed diagnosis of CH and a minimum period of follow-up of 1 year were included. Patients with Down syndrome, infants born at <35 weeks of gestation, and babies with TORCH (Toxoplasma gondii, Other viruses [HIV, measles, etc.], Rubella, Cytomegalovirus, and Herpes simplex) infections were subsequently excluded from the study. Results Of the subjects with CH, 39% had associated extrathyroidal anomalies (ETAs); among these, 25% had a single anomaly. A significant proportion of Arab males were affected by CH as compared to other ethnic groups. Dyshormonogenesis was the commonest aetiological cause (55%) of CH. Males with an ectopic lingual thyroid gland had significant ETAs as compared to females of the same cohort. The most common ETAs were congenital heart disease (16%), followed by urogenital tract anomalies (14%). Conclusions Detection of a high rate and variability of ETAs associated with CH necessitates the formulation of a structured screening programme including appropriate clinical, laboratory, and imaging tools to detect ETAs at an earlier stage.

Identification of a Novel Homozygous INSR Variant in a Patient with Rabson-Mendenhall Syndrome from the United Arab Emirates.

BACKGROUND/AIMS: This study aimed to identify, clinically and molecularly, the causality of Rabson-Mendenhall syndrome in an Emirati family. It is one of the monogenic syndromes of abnormal glucose homeostasis, which result from insulin receptor defects. METHODS: A novel nonsynonymous variant in the INSR gene was uncovered by whole exome sequencing and confirmed using Sanger sequencing in the patient and his parents. Various in silico tools were utilized to analyze the functional consequences of the variant. RESULTS: Results revealed a previously unreported INSR variant in the family: c.421C>T (p.Arg141Trp). Homozygosity for the variant was found in the patient, while both parents were heterozygous. CONCLUSION: The nonsynonymous protein change hit a highly conserved arginine residue in the insulin-binding α-subunit of the receptor and was deemed 'functionally damaging' by a myriad of bioinformatics tools. This report is a step forward along the way of achieving a better molecular and clinical characterization of Rabson-Mendenhall syndrome.

Neonatal Graves' disease with unusual metabolic association from presentation to resolution.

Neonatal Graves' disease is a rare disorder seen in 1 in 25,000 births and in 1% of the offspring of mothers with either established or cured Graves' disease. This is due to transplacental passage of thyroid-stimulating immunoglobulins (TSIs). A higher TSI titre in maternal serum makes hyperthyroidism more likely in the fetus or newborn; however, not all fetuses born by women with positive TSIs develop overt hyperthyroidism. In spite of its rarity, its serious nature (if not treated) and its association with multisystem abnormalities justifies careful clinical screening and management. We report a preterm 30 weeks neonate with neonatal thyrotoxicosis secondary to untreated maternal Graves' disease who, in addition to the typical hyperthyroidism symptoms, had unusual metabolic associations of neonatal cholestasis and hyperammonaemia. The patient was treated accordingly with a good response. This report supports previous reports on the association between neonatal hyperthyroidism and cholestatic liver disease. However, it is the second case report to describe the unusual association of hyperammonaemia and neonatal Graves' disease.