Type II diabetes and impaired glucose tolerance due to severe hyperinsulinism in patients with 1p36 deletion syndrome and a Prader-Willi-like phenotype

BACKGROUND: Deletion of the subtelomeric region of 1p36 is one of the most common subtelomeric deletion syndromes. In monosomy 1p36, the presence of obesity is poorly defined, and glucose metabolism deficiency is rarely reported. However, the presence of a typical Prader-Willi-like phenotype in patients with monosomy 1p36 is controversial. CASE PRESENTATION: In this report, we describe two female patients, one who is 6 years 2 months of age and another who is 10 years 1 month of age, both referred to our hospital for obesity and a Prader-Willi-like phenotype. These patients presented with severe obesity (body mass index [BMI] was 26.4 and 27.7, respectively), hyperphagia and developmental delay. Analysis of basal hormone levels showed normal thyroid function and adrenal function but considerable basal hyperinsulinism (the insulin levels were 54.5 and 49.2 μU/ml, respectively). In patient 1, glycaemia was 75 mg/dl (HOMA-R 10.09), and the HbA1c level was 6.1%; in patient 2, glycaemia was 122 mg/dl, and the HbA1c level was 6.6% (HOMA-R 14.82). An oral glucose tolerance test demonstrated impaired glucose tolerance and diabetes mellitus with marked insulin resistance (the peak insulin level for each patient was 197 and 279 μU/mL, respectively, while the 120’ insulin level of each patient was 167 and 234 μU/mL, respectively). CONCLUSION: some patients with monosomy 1p36 may show Prader-Willi-like physical and physiologic characteristics such as obesity and hyperinsulinism with impaired glucose metabolism, which can cause type II diabetes mellitus. Further studies are necessary to evaluate these findings

Evans syndrome and antibody deficiency: an atypical presentation of chromosome 22q11.2 deletion syndrome

We report a case of an 8-year-old male patient with Evans syndrome and severe hypogammaglobulinemia, subsequently in whom the 22q11.2 deletion syndrome (22q11.2 DS) was diagnosed. No other clinical sign of 22q11.2 DS was present with the exception of slight facial dysmorphism. The case is of particular interest because it suggests the need to research chromosome 22q11.2 deletion in patients who present with autoimmune cytopenia and peculiar facial abnormalities, which could be an atypical presentation of an incomplete form of 22q11.2 DS

Agenesis of internal carotid artery associated with isolated growth hormone deficiency: A case report and literature review

BACKGROUND: Agenesis of the internal carotid artery (ICA) is a rare congenital abnormality, sporadically reported to be associated with a combined congenital hypopituitarism. Nevertheless, only a few cases have been extensively described, and none of these have been characterized by an isolated growth hormone (GH) deficiency. CASE PRESENTATION: Here, we describe a 17-year old boy referred to our hospital for fatigue, decreased muscle strength and severe headache reported after the cessation of rhGH treatment for a GH deficiency diagnosed at the age of 2 years and 3 months. Magnetic resonance imaging (MRI) showed an adenohypophyseal hypoplasia with a lack of posterior pituitary hyperintensity, whereas MRI angiography indicated the absence of a normal flow void in the left ICA. Endocrinological tests confirmed the GH deficiency (GH peak after growth-hormone-releasing hormone (GHRH) + arginine: 2.42 ng/mL) with a very low IGF-I value (31 ng/mL) and normal function of other pituitary axes. CONCLUSION: To the best of our knowledge this is the first confirmed case of an isolated GH deficiency in a patient with ICA agenesis. The presence of an isolated pituitary deficit is unlike to be considered only as an effect of hemodynamic mechanism, suggesting a role for genetic factor(s) as a common cause of these two rare birth defects. Further studies could clarify this issue and the underlying mechanisms to better understand the etiopathogenetic characteristics of this disorder. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12902-015-0037-y) contains supplementary material, which is available to authorized users

Long-term auxological and endocrinological evaluation of patients with 9p trisomy: a focus on the growth hormone-insulin-like growth factor-I axis

BACKGROUND: Trisomy 9p is an uncommon anomaly characterised by mental retardation, head and facial abnormalities, congenital heart defects, kidney abnormalities, and skeletal malformations. Affected children may also show growth and puberty retardation with delayed bone age. Auxological and endocrinological data are lacking for this syndrome. METHODS: We describe three girls and one boy with 9p trisomy showing substantial growth failure, and we evaluate the main causes of their short stature. RESULTS: The target height was normal in all families, ranging from 0.1 and -1.2 standard deviation scores (SDS). The patients had a low birth-weight (from -1.2 to -2.4 SDS), birth length (from -1.1 to -3.2 SDS), and head circumference (from -0.5 to -1.6 SDS). All patients presented with substantial growth (height) retardation at the time of 9p trisomy diagnosis (from -3.0 to -3.8 SDS).The growth hormone stimulation test revealed a classic growth hormone (GH) deficiency (GHD) in patients 1, 3, and 4. In contrast, patient 2 was determined to have a GH neurosecretory dysfunction (GHNSD). The plasma concentrations of IGF-I and IGFBP-3 were low in all patients for their ages and sexes (from -2.0 to -3.4 SDS, and from -1.9 to -2.8 SDS, respectively).The auxological follow-up showed that those patients who underwent rhGH treatment exhibited a very good response to the GH therapy, whereas patients 3 and 4, whose families chose not to use rhGH treatment, did not experience any significant catch-up growth. CONCLUSIONS: GH deficiency appears to be a possible feature of patients with 9p trisomy syndrome. These patients, particularly those with growth delays, should be evaluated for GH secretion

Spheroids from equine amnion mesenchymal stem cells: an in vitro study

Background: Equine amnion mesenchymal stem cells (EAMSCs) from amnion isolated after the foal birth represented an alternative source of easy collection of mesenchymal cells used in equine regenerative medicine. Methods: These cells grown as 2D culture in α-MEM medium supplemented with EGF were differentiated in adipogenic, chondrogenic and osteogenic cells. Half a million cells as pellet were left in 15ml tubes with the same differentiation media for 20 days. After the pellets were collected, embedded in paraffin for morphological study. Results: 2D culture showed EAMSCs with an embryonic phenotype (C-kit+, CD105+, Oct-4+) and a differentiation potential in adipogenic, chondrogenic and osteogenic multipotent cells. By a reproducible method of 3D culture, at day 20 the Authors evidenced a formation of small aggregated spheroids gradually gathering. In cross sections the surface of spheroid evidenced flattened cells embedded in a red matrix by Alizarin staining and occasionally a core of calcium precipitation. A network of apoptotic or necrotic cells in a not mineralized matrix was present into the center of nodules. The 3D spheroids appeared larger (mean diameter of 605±53 µm for gathering spheroids and 1486±79 µm for spheroids already gathered) than those from standard monolayer cultures (mean diameter of 200 ± 73 µm). Conclusions: EAMSCs cultured in 3D method preserve their in vitro multipotent differentiation than adherent 2D culture method. These EAMSCs included in extracellular matrix not mineralized at day 20 seem to be a good source of MSCs for tissue repair and regeneration in equine medicine

A new case of de novo 6q24.2-q25.2 deletion on paternal chromosome 6 with growth hormone deficiency: A twelve-year follow-up and literature review

BACKGROUND: Deletions on the distal portion of the long arm of chromosome 6 are relatively uncommon, and only a small number occurs in the paternal copy, causing growth abnormalities. As a result, extensive clinical descriptions are lacking. CASE PRESENTATION: We describe a male of Italian descent born at 35 weeks by elective caesarean delivery presenting hypoplastic left colon, bilateral inguinal hernia, dysplastic tricuspid and pulmonary valves, premature ventricular contractions, recurrent otitis media, poor feeding, gastro-oesophageal reflux, bilateral pseudopapilledema, and astigmatism. He also showed particular facial dysmorphisms and postnatal growth failure. Early psychomotor development was mildly delayed. At 3.75 years, he was evaluated for severe short stature (−2.98 SD) and delayed bone age. He showed an insulin-like growth factor 1 concentration (IGF-1) in the low-normal range. Growth hormone stimulation tests showed a low response to clonidine and insulin. Magnetic resonance imaging showed hypophyseal hypoplasia. Genetic evaluation by Single Nucleotide Polymorphism arrays showed a de novo 6q24.2-q25.2 deletion on paternal chromosome 6. CONCLUSION: We confirm that this is a new congenital malformation syndrome associated with a deletion of 6q24.2-q25.2 on paternal chromosome 6. We suggest evaluating the growth hormone axis in children with 6q24.2-q25.2 deletions and growth failure

Bone Mineral Status in Children and Adolescents with Klinefelter Syndrome

Objective. Klinefelter syndrome (KS) has long-term consequences on bone health. However, studies regarding bone status and metabolism during childhood and adolescence are very rare. Patients. This cross-sectional study involved 40 (mean age: 13.7±3.8 years) KS children and adolescents and 80 age-matched healthy subjects. For both patient and control groups, we evaluated serum levels of ionised and total calcium, phosphate, total testosterone, luteinising hormone, follicle stimulating hormone, parathyroid hormone (PTH), 25-hydroxyvitamin D (25(OH)D), 1,25-dihydroxyvitamin D, osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline concentrations. We also calculated the z-scores of the phalangeal amplitude-dependent speed of sound (AD-SoS) and the bone transmission time (BTT). Results. KS children and adolescents showed significantly reduced AD-SoS (p<0.005) and BTT (p<0.0005) z-scores compared to the controls. However, KS patients presented significantly higher PTH (p<0.0001) and significantly lower 25(OH)D (p<0.0001), osteocalcin (p<0.05), and bone alkaline phosphatase levels (p<0.005). Interestingly, these metabolic bone disorders were already present in the prepubertal subjects. Conclusions. KS children and adolescents exhibited impaired bone mineral status and metabolism with higher PTH levels and a significant reduction of 25-OH-D and bone formation markers. Interestingly, this impairment was already evident in prepubertal KS patients. Follow-ups should be scheduled with KS patients to investigate and ameliorate bone mineral status and metabolism until the prepubertal ages

Different media and supplements modulate the clonogenic and expansion properties of rabbit bone marrow mesenchymal stem cells

<p>Abstract</p> <p>Background -</p> <p>Rabbits provide an excellent model for many animal and human diseases, such as cardiovascular diseases, for the development of new vaccines in wound healing management and in the field of tissue engineering of tendon, cartilage, bone and skin.</p> <p>The study presented herein aims to investigate the biological properties of bone marrow rabbit MSCs cultured in different conditions, in order to provide a basis for their clinical applications in veterinary medicine.</p> <p>Findings -</p> <p>MSCs were isolated from 5 New Zealand rabbits. Fold increase, CFU number, doubling time, differentiation ability and immunophenotype were analyzed.</p> <p>With the plating density of 10 cells/cm²the fold increase was significantly lower with DMEM-20%FCS and MSCs growth was significantly higher with αMEM-hEGF. The highest clonogenic ability was found at 100 cell/cm²with MSCBM and at 10 cell/cm²with M199. Both at 10 and 100 cells/cm², in αMEM medium, the highest CFU increase was obtained by adding bFGF. Supplementing culture media with 10%FCS-10%HS determined a significant increase of CFU.</p> <p>Conclusion -</p> <p>Our data suggest that different progenitor cells with differential sensitivity to media, sera and growth factors exist and the choice of culture conditions has to be carefully considered for MSC management.</p