31 research outputs found
Psychosocial Health and Lifestyle Behaviors in Young Adults Receiving Renal Replacement Therapy Compared to the General Population:Findings From the SPEAK Study
Continually improving standards of care:The UK Renal Registry as a translational public health tool
UK Renal Registry 18th Annual Report:Chapter 4 Demography of Patients Receiving Renal Replacement Therapy in Paediatric Centres in the UK in 2014
UK Renal Registry 18th Annual Report:Chapter 10 Clinical, Haematological and Biochemical Parameters in Patients Receiving Renal Replacement Therapy in Paediatric Centres in the UK in 2014: National and Centre-specific Analyses
The HNF4A R76W mutation causes atypical dominant Fanconi syndrome in addition to a β cell phenotype
types: JOURNAL ARTICLEMutation specific effects in monogenic disorders are rare. We describe atypical Fanconi syndrome caused by a specific heterozygous mutation in HNF4A. Heterozygous HNF4A mutations cause a beta cell phenotype of neonatal hyperinsulinism with macrosomia and young onset diabetes. Autosomal dominant idiopathic Fanconi syndrome (a renal proximal tubulopathy) is described but no genetic cause has been defined.This article presents independent research supported by the National Institute for Health Research (NIHR) Exeter Clinical Research Facility. The research is funded by a Wellcome Trust Senior Investigator Award, (grant number 098395/Z/12/Z).Wellcome Trus
Continually improving standards of care: The UK Renal Registry as a translational public health tool
Gonadotrophin abnormalities in an infant with Lowe syndrome
Summary
This case, presenting with bilateral impalpable testes, illustrates the relevance of a broad differential disorders of sex development case management. It provides new insights on hypothalamic–pituitary–gonadal (HPG) axis and testicular function abnormalities in the multisystem disorder of Lowe syndrome. Lowe syndrome, also known as oculocerebrorenal syndrome, is a rare disorder characterised by eye abnormalities, central nervous system involvement and proximal renal tubular acidosis. There are a handful of reports of pubertal delay, infertility and cryptorchidism in Lowe syndrome. Biochemistry aged 72 h: testosterone 6.4 nmol/L, LH <0.5 IU/L and FSH <0.5 IU/L. Gonadotropin-releasing hormone stimulation test identified significantly raised baseline LH = 45.4 IU/L (contrasts with earlier undetectable LH), with a 20% increase on stimulation, while baseline FSH = 4.3 IU/L with no increase on stimulation. Day 14 HCG stimulation test produced an acceptable 50% increase in testosterone. The constellation of further abnormalities suggested Lowe syndrome: hypotonia, bilateral cataracts (surgical extraction and intraocular lens implantation) and renal tubular acidosis (microscopic haematuria, hypercalciuria, proteinuria, generalised aminoaciduria, hypophosphataemia and metabolic acidosis). DNA sequencing identified de novo hemizygous frameshift mutation OCRL c.2409_2410delCT in exon 22. Interpretation of initial and repeat GnRH and HCG testing indicates the likelihood of testicular failure. Partial testicular descent occurred but left orchidopexy was required. Improving long-term gonadal function in Lowe syndrome assumes increased importance for current cohorts as advances in renal replacement therapy have greatly improved life expectancy. Noting HPG axis abnormalities in Lowe syndrome in infancy can identify cases requiring increased surveillance of pubertal progress for earlier detection and management.
Learning points:
Clinical endocrine problems in Lowe syndrome has been reported, but has focused on abnormalities in adolescence and young adulthood: pubertal delay and infertility.
We present an infant with isolated LH elevation at baseline and on GnRH stimulation testing who also had bilateral impalpable testes.
Early testing of the HPG axis in patients with Lowe syndrome may help predict gonadal abnormalities from a younger age, which will enhance the overall case management into adolescence.
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