Purpose
Among genetic causes of combined pituitary hormone deficiency (CPHD), mutations of genes coding for transcription factors involved in pituitary development have been implicated. Congenital ...CPHD is a rare disease; therefore, it is important to expand the knowledge about incidence and regional distribution of specific mutations. The aim of this paper is to report results of genetic analyses of adult Slovenian patients with CPHD.
Methods
Twenty-three adult Slovenian patients with early childhood onset CPHD were included in the study. Blood samples were collected through the GENHYPOPIT network to assess possible mutations of six genes (
PROP1/HESX1/LHX4/LHX3/POU1F1
) involved in the pituitary development following an established algorithm.
Results
In seven out of 23 patients (30%) a specific mutation in genes encoding pituitary transcription factors was discovered. In five patients, two different mutations of the
PROP1
gene (c.150delA and c.301-302delAG) were identified. One patient was heterozygous for a missense variant in the
LHX4
gene. Additionally, one patient was positive for a mutation in the gene coding for prokineticin receptor-2.
Conclusions
Our study confirms that the two most common mutations of the
PROP1
gene globally are also the most frequent mutations in the cohort of adult Slovenian patients with CHPD. Other mutations of pituitary transcription factor genes are extremely rare.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background: In cases of normotensive patients, hypokalemia with metabolic alkalosis is most frequently caused by repeated vomiting or diuretics abuse, and rarely by tubulopathies, e.g., Bartter or ...Gitelman syndrome (GS). Case report: An adolescent girl who was repeatedly examined due to collapses and cramps in the hands. A characteristic set of metabolic abnormalities for tubulopathies was discovered in an acute stress situation with inapetence. Proper diet and supplementation with potassium and magnesium was needed for maintaining electrolyte balance of the patient. Conclusions: In cases of unexplained hypokalemia and metabolic alkalosis associated with a normal or low blood pressure a tubulopathy, e.g., Gitelman syndrome, must be excluded. The identification and recognition of correct diagnosis is extremely important since a proper treatment can reduce the risk of life-threatening events, e.g. arrhythmias.
Patients with rare diseases face health disparities and are often challenged to find accurate information about their condition. We aimed to use the best available evidence and community partnerships ...to produce patient education materials for congenital hypogonadotropic hypogonadism (CHH) and the olfacto-genital (Kallmann) syndrome (i.e., CHH and defective sense of smell), and to evaluate end-user acceptability. Expert clinicians, researchers and patients co-created the materials in a multi-step process. Six validated algorithms were used to assess reading level of the final product. Comprehensibility and actionability were measured using the Patient Education Materials Assessment Tool via web-based data collection. Descriptive statistics were employed to summarize data and thematic analysis for analyzing open-ended responses. Subsequently, translation and cultural adaption were conducted by clinicians and patients who are native speakers.
Co-created patient education materials reached the target 6
grade reading level according to 2/6 (33%) algorithms (range: grade 5.9-9.7). The online survey received 164 hits in 2 months and 63/159 (40%) of eligible patients completed the evaluation. Patients ranged in age from 18 to 66 years (median 36, mean 39 ± 11) and 52/63 (83%), had adequate health literacy. Patients scored understandability at 94.2% and actionability at 90.5%. The patient education materials were culturally adapted and translated into 20 languages (available in Additional file 1).
Partnering with patients enabled us to create patient education materials that met patient- identified needs as evidenced by high end-user acceptability, understandability and actionability. The web-based evaluation was effective for reaching dispersed rare disease patients. Combining dissemination via traditional healthcare professional platforms as well as patient-centric sites can facilitate broad uptake of culturally adapted translations. This process may serve as a roadmap for creating patient education materials for other rare diseases.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The study attempts to evaluate the short-term efficacy and safety of an artificial pancreas at improving glucose control and reducing nocturnal hypoglycemia. The results indicate that diabetic ...patients treated with a sensor-augmented insulin pump have less nocturnal hypoglycemia and tighter glucose control.
Autoimmune polyglandular syndrome type 1 (APS-1) is an autosomal recessive disorder, caused by mutations in the AIRE gene. The major components of APS-1 are chronic mucocutaneous candidiasis (CMC), ...hypoparathyroidism (HP) and Addison's disease (AD). Clinical, genetic and immunological characteristics of Slovenian paediatric APS-1 patients were investigated.
Existing medical records of 15 APS-1 patients were rewieved, when necessary, additional clinical and laboratory investigations were issued. AIRE gene analysis was performed to identify causative mutations, and autoantibodies against type I interferons were measured by luminescence immunoprecipitation system.
Patients had one to eight different manifestations of the disease. CMC was present in all, HP in 12/15 (80 %) and AD in 8/15 (53 %) patients. Growth retardation, due to hyposomatotropism, growth hormone resistance, autoimmune thyroiditis, corticosteroid treatment, malabsorption or secretory failure of exocrine pancreas, was observed in altogether 7 (46 %) patients. Six different AIRE gene mutations were detected and p.R257X mutation was present in 63.3 % of pathological alleles. Antibodies against type I interferons were detected in all patients.
APS-1 is a rare disorder with a broad spectrum of clinical manifestations, which, if unrecognized or inadequately treated may be fatal. AIRE gene mutational analysis and autoantibodies against type I interferons are important in early identification of the disease. The aetiology of growth retardation was shown to be extremely diverse, frequently caused by less characteristic manifestations. APS-1 may affect patients' quality of life in numerous ways, and may cause great psychosocial burden leading to depression and suicidal thoughts even in paediatric patients.
Background: In cases of normotensive patients, hypokalemia with metabolic alkalosis is most frequently caused by repeated vomiting or diuretics abuse, and rarely by tubulopathies, e.g., Bartter or ...Gitelman syndrome (GS). Case report: An adolescent girl who was repeatedly examined due to collapses and cramps in the hands. A characteristic set of metabolic abnormalities for tubulopathies was discovered in an acute stress situation with inapetence. Proper diet and supplementation with potassium and magnesium was needed for maintaining electrolyte balance of the patient. Conclusions: In cases of unexplained hypokalemia and metabolic alkalosis associated with a normal or low blood pressure a tubulopathy, e.g., Gitelman syndrome, must be excluded. The identification and recognition of correct diagnosis is extremely important since a proper treatment can reduce the risk of life-threatening events, e.g. arrhythmias.
Objective The aim of this study was to determine whether an expanded newborn screening programme, which is not yet available in Slovenia, would have detected the first two patients with medium-chain ...acyl-CoA dehydrogenase (MCAD) deficiency in the country. Two novel ACADM mutations are also described. Methods Both patients were diagnosed clinically; follow-up involved analysis of organic acids in urine, acylcarnitines in dried blood spots, and genetic analysis of ACADM . Cut-off values of acylcarnitines in newborns were established using analysis of 10,000 newborns in a pilot screening study. Results In both patients, analysis of the organic acids in urine showed a possible β-oxidation defect, while the specific elevation of acylcarnitines confirmed MCAD deficiency. Subsequent genetic analysis confirmed the diagnosis; both patients were compound heterozygotes, each with one novel mutation (c.861 + 2T > C and c.527_533del). The results from a retrospective analysis of newborn screening cards clearly showed major elevations of MCAD-specific acylcarnitines in the patients. Conclusions An expanded newborn screening programme would be beneficial because it would have detected MCAD deficiency in both patients before the development of clinical signs. Our study also provides one of the first descriptions of ACADM mutations in Southeast Europe.
Uvod. Osteogenesis imperfecta (OI) je vzročno heterogena bolezen, katere značilnost je osteoporoza v otroštvu. Pri vseh opisanih bolnikih s podtipom OI tipa V je vzrok bolezni ista mutacija c.-14C>T ...gena IFITM5. Kljub temu med bolniki obstaja izrazita fenotipska variabilnost v klinični sliki, toda opisan je le dober odgovor na zdravljenje z bisfosfonati.
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