Endocrine Abstracts

Background: Growth Hormone Insensitivity (GHI) is characterised by short stature and functional IGF-I deficiency associated with normal/elevated GH levels. Marked genetic and phenotypic heterogeneity exist, and heritable defects in GH-IGF-I axis associated pathways account for mild-moderate to severe GHI. We report non-consanguineous twin brothers who present with short stature and bi-allelic mutations in QSOX2 encoding a nuclear membrane protein. Genome-wide associat...

Background: PAPP-A2 is a protease which helps to release IGF-1 from a ternary complex by cleaving the IGF binding proteins (IGFBP-3 and -5). Free IGF-1 subsequently binds to its receptor resulting in cell proliferation and growth. Homozygous loss-of-function PAPPA2 mutations lead to low IGF-1 bioavailability and postnatal short stature (SS). Recombinant human IGF-1 (rhIGF-1) treatment improves height SDS in few patients. We report a patient with SS and high plasma tot...

Background: Diabetic retinopathy is a frequent cause of vision loss in young adults. NICE guidelines require services to offer annual retinal screening to all diabetic children aged ≥12 years. A local 2009–2010 audit identified 57% underwent screening but only 16% had results documented with the paediatric diabetes service, both areas requiring improvement. In 2011, the paediatric diabetes service formulated a standard operating procedure with the eye-screening prog...

Although pituitary abnormalities are the most commonly reported endocrine feature in septo-optic dysplasia, other endocrine abnormalities have not been described so far. We present a case of septo-optic dysplasia (SOD) and pituitary dysfunction, complicated by X-linked adrenoleucodystrophy (X-ALD) and primary adrenal insufficiency.A 4-year-old boy was referred with hypoglycaemic episodes and seizures during intercurrent illnesses. He had a history of pol...

Section 1: Case history: A 10-year-old girl presented with significant postnatal growth failure. Her birth weight was normal (–0.15SDS) but poor growth was observed from a few months of age. She had no other symptoms. On examination, height was –3.4SDS and head circumference –1.6SDS. She had no dysmorphic features and normal development. Section 2: Investigations: Baseline serum analyses were unremarkable. Karyotype was normal (46XX). Bone age was delayed by 2.5...

Global encephalopathy is a rare complication of Hashimoto’s thyroiditis. It typically presents with seizures, ataxia and tremors and responds to steroid therapy. Limbic encephalitis (LE) is even less well described in paediatric population. It presents with medio-temporal lobe symptoms (memory impairment, temporal lobe seizures and disturbances of affect) caused by inflammation within the hippocampus, amygdala, hypothalamus, insular and cingulate cortex. LE most commonly ...

Background: GH insensitivity (GHI) presents with growth failure, IGF-1 deficiency and normal/elevated GH (basal >5 μg/l and/or peak >10 μg/l). GHI encompasses a spectrum of clinical and biochemical abnormalities. Associations between phenotypic characteristics and genetic defects remain obscure.Objective: Identify phenotypic predictors of underlying genetic defects in GHI.Methods: In total of 102 children (62M) me...

Background: Pathogenic IGFI gene mutations causing childhood growth failure are extremely rare. Only five autosomal recessive mutations, one IGFI copy number variant and two heterozygous frameshift mutations are reported. Heterozygous missense IGFI mutations haven’t previously been described.Objectives: To identify and functionally characterise a novel missense IGFI variant in a patient with postnatal growth failu...

Background: GH Insensitivity (GHI) is usually caused by mutations in the GH receptor (GHR). Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c. 618+792A>G). Inclusion of this 108bp pseudoexon is predicted to lead to in-frame insertion of 36 amino acid residues in the dimerization domain of the GHR. This results in defective trafficking rather than impaired signalling, causing partial loss-of-function and moderat...

Background: Growth Hormone Insensitivity is usually caused by mutations in the Growth Hormone receptor (GHR). Patients present with short stature, high GH levels, low IGF-I levels and typical Laron syndrome facial features. Our centre previously described the first GHR pseudoexon mutation (42700896A>G, c.618+792A>G). The inclusion of this pseudoexon is predicted to cause in-frame insertion of 36 amino acid residues between exons 6 and 7. This insertion in the ...