ABSTRACT
Familial glucocorticoid deficiency (FGD) is an autosomal recessive disorder characterized by low cortisol levels despite elevated adrenocorticotropin (ACTH). Mineralocorticoid secretion is classically normal. Clinical manifestations are secondary to low cortisol levels (recurrent hypoglycemia, chronic asthenia, failure to thrive, seizures) and high levels of ACTH (cutaneous-mucosal hyperpigmentation). FGD is often caused by mutations in the ACTH melanocortin 2 receptor gene (MC2R, 18p11.21, FGD type 1) or melanocortin receptor 2 accessory protein gene (MRAP, 21q22.11, FGD type 2). But mutations have also been described in other genes: the steroidogenic acute regulatory protein (STAR, 8q11.2q13.2, FGD type 3), nicotinamide nucleotide transhydrogenase (NNT, 5p12, FGD type 4) and thioredoxin reductase 2 genes (TXNRD2, 22q11.21, FGD type 5). We report the case of a 3-year-old boy recently diagnosed with FGD type 4 due to a novel mutation in NNT gene. A homozygous variant in exon 18 of the NNT gene, NM_012343.3:c.2764C>T, p.(Arg922*), determines a stop codon and, consequently, a non-functional truncated protein or absence of protein due to the nonsense-mediated decay (NMD) mechanism. We review the recent literature on NNT mutations and clinical presentations, which are broader than suspected. This disorder can result in significant morbidity and is potentially fatal if untreated. Precise diagnosis allows correct treatment and follow-up.
Subject(s)
Addison Disease , Adrenal Insufficiency , Male , Humans , Child, Preschool , Glucocorticoids/metabolism , Hydrocortisone , Adrenal Insufficiency/genetics , Addison Disease/genetics , Mutation , Adrenocorticotropic HormoneABSTRACT
BACKGROUND: Several immunisation candidates against RSV are in late-stage clinical trials. To evaluate the benefits of a potential vaccination programme, both economic and health benefits will be needed. Health benefits are usually measured in Health-related Quality of Life (HRQoL) loss using standardised questionnaires. However, there are no RSV-specific questionnaires validated for children under 2 years, in whom most RSV episodes occur. Therefore, HRQoL estimates are taken from literature or inadequate tools. We determined HRQoL loss and direct costs due to an RSV episode in children younger than 2 years and their caregivers during a month of follow up, using a new questionnaire administered online. METHODS: An observational prospective multicentre surveillance study was conducted in children aged younger than two years. Children were recruited from 8 primary care centres and 1 hospital in the Valencia region and Catalonia (Spain). RSV-positive cases were obtained by immunochromatographic test. HRQoL was assessed using a new ad-hoc 38 item-questionnaire developed. Parents of infected children completed 4 questionnaires at four timepoints (day 0, 7, 14 and 30) after diagnosis. RESULTS: 117 children were enrolled in the study and 86 (73.5%) were RSV + . Median (interquartile range; IQR) scores were 0.52 (0.42-0.68), 0.65 (0.49-0.79), 0.82 (0.68-0.97) and 0.94 (0.81-1), for days 0, 7, 14 and 30, respectively. Compared to total recovery (Q30), HRQoL loss was 37.5%, 31.5% and 8.9% on days 0, 7 and 14 since diagnosis of the disease. The total median cost per patient (including treatments) was 598.8 (IQR: 359.63-2425.85). CONCLUSIONS: RSV had almost 40% impact on HRQoL during the first week since onset of symptoms and the median cost per episode and patient was about 600. These results represent a substantial input for health-economic evaluations of future RSV-related interventions such as vaccination.
Subject(s)
Quality of Life , Respiratory Syncytial Virus Infections , Child , Humans , Infant , Parents , Prospective Studies , Respiratory Syncytial Virus Infections/epidemiology , Spain/epidemiologyABSTRACT
El síndrome McCune-Albright es una enfermedad rara de carácter esporádico, descrita por McCune y Albright en 1937. Está causada por la mutación del gen GNAS1, que estimula el crecimiento y la función de las glándulas endocrinas, los melanocitos y los osteoclastos. Tríada característica de displasia fibrosa poliostótica, alteraciones endocrinas múltiples y mancha café con leche
McCune-Albright syndrome is a rare sporadic disease, described by McCune and Albright in 1937. It is caused by the mutation of the GNAS1 gene, which stimulates the growth and function of the endocrine glands, melanocytes and osteoclasts. Triad characteristic: polyostotic fibrous dysplasia, multiple endocrine alterations and café-au-lait skin pigmentation
