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ABSTRACT: Acanthosis nigricans (AN) has been reported in association with severe skeletal dysplasias due to activating mutations in FGFR3, including thanatophoric dysplasia, severe achondroplasia (ACH) with developmental delay and AN (SADDAN syndrome), and Crouzon syndrome with AN. There are isolated reports of patients with ACH and AN. In this series, we report clinical and biochemical data on five male patients, four with ACH and one with hypochondroplasia (HCH), who developed AN without SADDAN.
We compared the results of a 1.75 g/kg oral glucose tolerance test performed in patients with ACH/HCH and AN with age-, sex-, and puberty-matched short children. Three of the patients were treated with recombinant human GH (dose range, 45-50 microg/kg/d), one patient had discontinued treatment 6 months before presentation, and one had never been treated. All patients had a fasting plasma glucose of less than 6 mmol/liter, and no patient had a plasma glucose greater than 7.8 mmol/liter at 2 h after ingestion of a glucose load. Although body mass index was higher in patients with skeletal dysplasia (28.9 +/- 7.3 vs. 20 +/- 0.6 kg/m(2); P = 0.01), mean fasting plasma insulin concentration was greater in controls (14.4 +/- 4.8 vs. 6.0 +/- 4.5 mU/liter; P = 0.03), as was homeostasis assessment index for insulin resistance (2.5 +/- 0.9 vs. 1.17 +/- 0.8; P = 0.05).
Our findings suggest that the development of AN in patients with ACH/HCH is not due to insulin insensitivity either on its own or secondary to treatment with recombinant human GH. Whether the AN is due to altered melanocyte function in these individuals remains to be established.
The Journal of clinical endocrinology and metabolism 08/2009; 94(10):3959-63. · 6.50 Impact Factor
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ABSTRACT: Introduction: Urinary tract infections (UTIs) are a common cause of morbidity in childhood with potential for renal scarring and reflux nephropathy which can lead to hypertension and end-stage renal failure. Aim: The aim of this study was to investigate the relationship between the infecting organism and any underlying anomalies of the urinary tract which may predispose to the development of infections and which may alter the management of children with UTIs. Methods and results: A total of 72 cases of UTI were recorded retrospectively (in-and outpatients), with ages ranging from 3 days to 48 months (mean 9.5, median 5 months). Fifty seven (79%) of patients had their first reported urinary tract infection under the age of 1 year.. Fifty eight (80.6%) were E. coli infections. These presented at an older age than non-E. coli infections. Investigations were abnormal in 31 (43%) cases. The mean age for first infection in patients with abnormal investigations was 7.7 months (median 2 months), younger than those with no renal tract abnormalities. Organisms other than E. coli were rarely found when no significant abnormalities were detected with investigation by US and MCUG and this was a statistically significant difference (p<0.001). Renal scarring was identified in 10 (13.9%) patients. Discussion: This study confirms that non-E. coli UTI is associated with underlying renal pathology and that early infections with any organism are more likely to be associated with underlying abnormalities. We also outline an algorithm based on the recent NICE 2007 guidelines which will be adopted by the Paediatric Department, Mater Dei Hospital for the investigation of UTI.
22 Malta Medical Journal Volume. 07/2008; 20.
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James P G Turton,
Rachel Reynaud,
Ameeta Mehta, John Torpiano,
Alexandru Saveanu,
Kathryn S Woods,
Anatoly Tiulpakov,
Vera Zdravkovic,
Jill Hamilton,
Simon Attard-Montalto,
Ray Parascandalo,
Cecil Vella,
Peter E Clayton,
Stephen Shalet,
John Barton,
Thierry Brue,
Mehul T Dattani
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ABSTRACT: Mutations within the gene encoding the pituitary-specific transcription factor POU1F1 are associated with combined pituitary hormone deficiency (CPHD). Most of the affected individuals manifest GH, prolactin, and TSH deficiency.
We have now screened 129 individuals with CPHD and isolated GH deficiency for mutations within POU1F1.
Causative mutations were identified in 10 of 129 individuals (7.8%). Of these, five patients harbored the dominant negative R271W mutation, which is a well-recognized mutational hot spot. We have also identified a second frequently occurring mutation, E230K, which appears to be common in Maltese patients. Additionally, we describe two novel mutations within POU1F1, an insertion of a single base pair (ins778A) and a missense mutation (R172Q). Functional studies have revealed that POU1F1 (E230K) is associated with a reduction in transactivation, although DNA-binding affinity is similar to the wild-type protein. On the other hand, POU1F1 (R172Q) is associated with a reduction in DNA binding and transactivation, whereas POU1F1 (ins778A) is associated with loss of DNA binding and a reduction in transactivation.
Our data suggest that the phenotype associated with POU1F1 mutations may be more variable, with the occasional preservation of TSH secretion. Additionally, our data revealed POU1F1 mutations in three patients who were diagnosed as having ACTH deficiency but who, on further evaluation, were found to have normal cortisol secretion. Hence, elucidation of the genotype led to further evaluation of the phenotype, with the cessation of cortisol replacement that had been commenced unnecessarily. These data reflect the importance of mutational analysis in patients with CPHD.
Journal of Clinical Endocrinology & Metabolism 09/2005; 90(8):4762-70. · 6.50 Impact Factor
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Journal of pediatric endocrinology & metabolism: JPEM 05/2004; 17(4):663-4. · 0.88 Impact Factor
