Front Endocrinol (Lausanne)
April 2023
Objective: To analyze the mutational spectrum, clinical characteristics, genotype-phenotype correlations, testicular adrenal rests tumor prevalence, and role of neonatal screening in congenital adrenal hyperplasia (CAH) patients from Slovakia and Slovenia.
Design And Methods: Data were obtained from 104 patients with CAH registered in Slovak and Slovenian databases. Low-resolution genotyping was performed to detect the most common point mutations.
Front Endocrinol (Lausanne)
December 2022
Background/aims: Central precocious puberty (CPP) is due to premature activation of the hypothalamic-pituitary-gonadal axis. It predominantly affects girls. CPP leads to lower final height (FH), yet the treatment benefit in girls between 6 and 8 years is equivocal.
View Article and Find Full Text PDFDifferences of sex development and maturation (SDM) represent a heterogeneous puzzle of rare conditions with a large genetic component whose management and treatment could be improved by an accurate classification of underlying molecular conditions, and next-generation sequencing (NGS) should represent the most appropriate approach. Therefore, we conducted a survey dedicated to the use and potential outcomes of NGS for SDM disorders diagnosis among the 53 health care providers (HCP) of the European Reference Network for rare endocrine conditions. The response rate was 49% with a total of 26 HCPs from 13 countries.
View Article and Find Full Text PDFKlinefelter syndrome is the most commonly reported sex chromosome abnormality. It is heavily underdiagnosed due to the substantial variability of clinical presentations but is generally characterized by small, firm testes, hypergonadotropic hypogonadism, and the absence of spermatogenesis. Most patients with Klinefelter syndrome have a 47,XXY genotype.
View Article and Find Full Text PDFPathogenic variants within the gene encoding the pituitary-specific transcription factor, POU class 1 homeobox 1 (), are associated with combined pituitary hormone deficiency (CPHD), including growth hormone, prolactin, and thyrotropin stimulating hormone deficiencies. The aim of the study was to identify genetic aetiology in 10 subjects with CPHD from four consanguineous Sudanese families. Medical history, as well as hormonal and radiological information, was obtained from participants' medical records.
View Article and Find Full Text PDFA Caucasian girl with consanguineous parents presented with early severe obesity and retinal dystrophy. A novel, homozygous gene truncating variant (c.1897C>T) in the gene confirmed the diagnosis of MORMS (OMIM #610156).
View Article and Find Full Text PDFProopiomelanocortin (POMC) deficiency is an extremely rare inherited autosomal recessive disorder characterized by severe obesity, adrenal insufficiency, skin hypopigmentation, and red hair. It is caused by pathogenic variants in the gene that codes the proopiomelanocortin polypeptide which is cleaved to several peptides; the most notable ones are adrenocorticotropic hormone (ACTH), alpha- and beta-melanocyte-stimulating hormones (-MSH and -MSH); the latter two are crucial in melanogenesis and the energy balance by regulating feeding behavior and energy homeostasis through melanocortin receptor 4 (MC4R). The lack of its regulation leads to polyphagia and early onset severe obesity.
View Article and Find Full Text PDF. Familial non-autoimmune autosomal dominant hyperthyroidism (FNAH) is a rare cause of childhood hyperthyroidism. It is caused by the thyroid-stimulating hormone receptor () gene variants.
View Article and Find Full Text PDFResistance to thyroid hormone beta (RTHβ) is a syndrome characterized by a reduced response of target tissues to thyroid hormones. In 85% of cases, a pathogenic mutation in the thyroid hormone receptor beta () gene is found. The clinical picture of RTHβ is very diverse; the most common findings are goiter and tachycardia, but the patients might be clinically euthyroid.
View Article and Find Full Text PDF3-methylglutaconic aciduria type 1 (3-MGA-I) (MIM ID #250950) is an ultra-rare, autosomal recessive organic aciduria, resulting from mutated gene, leading to the deficient 3-methylglutaconyl-CoA hydratase (3-MGH). Only around 40 cases are previously reported, caused by a spectrum of 10 mutations. The clinical spectrum of 3-MGA-I in children is heterogeneous, varying from asymptomatic individuals to mild neurological impairment, speech delay, quadriplegia, dystonia, choreoathetoid movements, severe encephalopathy, psychomotor retardation, basal ganglia involvement.
View Article and Find Full Text PDFDespite recent improvements in the composition of the diet, lower mineral bone density and overweight tendencies are incoherently described in patients with phenylketonuria (PKU). The impact of dietary factors and plasma phenylalanine levels on growth, BMI, body composition, and bone mineral density was investigated in our cohort of patients with hyperphenylalaninemia (HPA) with or without dietary treatment. The anthropometric, metabolic, BMI and other nutritional indicators and bone mineral density were compared between the group of 96 treated patients with PKU (58 classic PKU (cPKU) and 38 patients with moderate-mild PKU defined as non-classic PKU (non-cPKU)) and the untreated group of 62 patients with benign HPA.
View Article and Find Full Text PDFObjective: To investigate the effect of acute hyperglycemia on brain function in adolescents with type 1 diabetes (T1D).
Research Design And Methods: Twenty participants with T1D (aged 14.64 ± 1.
J Allergy Clin Immunol
May 2020
Background: Recent findings strongly support hematopoietic stem cell transplantation (HSCT) in patients with severe presentation of LPS-responsive beige-like anchor protein (LRBA) deficiency, but long-term follow-up and survival data beyond previous patient reports or meta-reviews are scarce for those patients who do not receive a transplant.
Objective: This international retrospective study was conducted to elucidate the longitudinal clinical course of patients with LRBA deficiency who do and do not receive a transplant.
Method: We assessed disease burden and treatment responses with a specially developed immune deficiency and dysregulation activity score, reflecting the sum and severity of organ involvement and infections, days of hospitalization, supportive care requirements, and performance indices.
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.
View Article and Find Full Text PDFKlin Padiatr
March 2019
Recurrent myocarditis is rare with only few reports having been published for paediatric cases. Repeated use of extracorporeal membrane oxygenation is also uncommon. In this paper we will present a very rare case of a 7-year old girl with recurrent fulminant myocarditis with heart failure requiring cardiopulmonary resuscitation and mechanical circulatory support with extracorporeal membrane oxygenation.
View Article and Find Full Text PDFObjective 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.
View Article and Find Full Text PDFBackground: Lipopolysaccharide-responsive, beige-like anchor protein (LRBA) deficiency is characterized by primary immunodeficiency and autoimmunity. Cancer may present another feature of LRBA deficiency. We describe a case history of a young adult with LRBA deficiency and two independent malignancies.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFAims: To evaluate the safety, efficacy and need for remote monitoring of the MD-Logic closed-loop system during short-term overnight use at home.
Methods: Seventy-five patients (38 male; aged 10-54 years; average A1c, 7.8% ± 0.
Background/aims: The HESX1 gene is essential in forebrain development and pituitary organogenesis, and its mutations are the most commonly identified genetic cause of septo-optic dysplasia (SOD). The PROP1 gene is involved in anterior pituitary cell lineage specification and is commonly implicated in non-syndromic combined pituitary hormone deficiency (CPHD). We aimed to assess the involvement of HESX1 and PROP1 mutations in a cohort of patients with SOD and CPHD.
View Article and Find Full Text PDFIntroduction: Osteogenesis imperfecta (OI) is etiologically heterogeneous disorder characterized by childhood osteoporosis. A subtype OI type V is caused by the same c.-14C>T mutation in the IFITM5 gene.
View Article and Find Full Text PDFIntroduction: 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.
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