. 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. So far, ...only around 40 families with FNAH have been reported. Patients with activating
variants demonstrated the same classical signs and symptoms of hyperthyroidism as seen in patients with Graves' disease. Since 2012, ablative therapy is recommended to avoid relapses of hyperthyroidism and its consequences.
. We presented a young adult male patient with a novel heterozygous
disease-causing variant p.Arg418Lys (c.1253G>A) in the exon 10, who presented with a mild but progressive FNAH, with a follow-up since infancy.
. Constantly suppressed TSH, including during the euthyreosis in childhood and hypothyreosis after iodine ablation therapy, suggested central dysregulation of the TSH secretion.
Resistance 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. The laboratory findings are almost pathognomonic with elevated free thyroxin (fT4) levels and high or normal thyrotropin (TSH) levels; free triiodothyronin (fT3) levels may also be elevated. We present three siblings with
mutation (heterozygous disease-variant c.727C>T, p.Arg243Trp); two of them also had hypercholesterolemia, while all three had several other clinical characteristics of RTHβ. This is the first description of the known Slovenian cases with RTHβ due to the pathogenic mutation in the
gene. Hypercholesterolemia might be etiologically related with RTHβ, since the severity of hormonal resistance varies among different tissues and hypercholesterolemia in patients with
variants might indicate the relatively hypothyroid state of the liver. We suggest that cholesterol levels are measured in all RTHβ patients.
Despite 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. Having compared the treated and untreated groups, there were normal outcomes and no statistically significant differences in BMI, body composition, and bone mineral density. Lower body height standard deviation scores were observed in the treated as compared to the untreated group (P < 0.001), but the difference was not significant when analyzing patients older than 18 years; however, cPKU adults were shorter compared to non-cPKU treated adults (P = 0.012). Interestingly, the whole-body fat was statistically higher in non-cPKU as compared to cPKU patients. In conclusion, the dietary treatment ensured adequate nutrition without significant consequences in BMI, body composition, and bone mineral density. A low protein diet may have delayed the growth in childhood, but the treated patients gained a normal final height. Mild untreated hyperphenylalaninemia characteristic for benign HPA had no negative physiological effect on bone mineral density.
3-methylglutaconic aciduria type 1 (3-MGA-I) (MIM ID #250950) is an ultra-rare, autosomal recessive organic aciduria, resulting from mutated AUH 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. Early dietary treatment with leucine restriction and carnitine supplementation may be effective in improving neurological state in pediatric patients with 3-MGA-I.
We presented a girl with 3-MGA-I due to novel AUH gene mutation (homozygous variant c.330 + 5G > A) and confirmed by almost undetectable 3-MGH-enzyme activity, who initially presented with central precocious puberty at an early age of 4.5 years.
Precocious puberty might be associated with the 3-MGA-I, as is reported previously in some other metabolic disorders that result in pathologic accumulation of metabolites or toxic brain damage. Therapy with GnRH agonist triptorelin effectively arrested pubertal development.
•Girl with 3-MGA-I presented with central precocious puberty.•Novel AUH gene mutation and almost undetectable 3-MGH-enzyme activity were detected.•GnRH agonist triptorelin effectively arrested pubertal development.•Precocious puberty is reported in some other metabolic disorders.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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.
Hipoglikemija je pogosta presnovna motnja pri novorojenčkih. Opredeljena je kot vrednost krvnega sladkorja pod 2,2 mmol/l v prvih 24 urah življenja in pod 2,6 mmol/l v starosti 24–48 ur. Večinoma je ...prehodna, medtem ko so podaljšane ali ponavljajoče se epizode povezane z dolgotrajnimi nevrološkimi posledicami. Novorojenčkom, ki so zdravi, donošeni in brez znakov hipoglikemije ter po normalno potekajoči nosečnosti in porodu, koncentracije krvnega sladkorja rutinsko ne merimo. Novorojenčkom s povečanim tveganjem za pojav hipoglikemije merimo koncentracijo krvnega sladkorja po prvem hranjenju, ki naj bo v prvi uri po rojstvu. Dodatne preiskave opravimo pri vztrajajoči hipoglikemiji (več kot 48 ur), če novorojenček s hipoglikemijo nima znanih dejavnikov tveganja za hipoglikemijo, pri novorojenčku z epileptičnimi krči, ki so posledica hipoglikemije, in če novo-rojenček za vzdrževanje normalnih vrednosti krvnega sladkorja potrebuje infuzijo z več kot 12–15 mg glukoze/kg/min. Najpogostejši vzrok vztrajajoče hipoglikemije pri novorojenčkih je hiperinzulinizem. Inzulin zavira lipolizo in tvorbo ketonskih teles. Možgani ostanejo brez nadomestnega vira energije, kar lahko vodi v nevrološke okvare. V prispevku opisujemo novorojenko z Beckwith-Wiede-mannovim sindromom, ki je imela vztrajajočo hipoglikemijo zaradi hiperinzulinizma in je bila zdravljena z oktreotidom.
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. Our main goal was to evaluate the effects of gonadotropin-releasing hormone analog (GnRHa) on FH and identify factors that predict FH.
In a retrospective study, children with CPP (12 boys, 81 girls) that reached FH were included. Their clinical data at diagnosis and up to their final height was compared by descriptive statistics among idiopathic (iCPP) (n=68) and non-idiopathic CPP (nCPP) and between GnRHa treated (n=48) and untreated (n=15) girls with iCPP. The treatment effect of body weight (BW) adjusted GnRHa dosing was evaluated. Univariate linear regression and step-wise multivariable regression including 48 girls with iCPP treated with GnRHa were performed to identify predicting factors for FH.
Children with idiopathic CPP (iCPP) reached higher FH (p=0.002) than children with non-idiopathic CPP. After the diagnosis, the treated group gained 7.0 cm more than the untreated group. Yet, attributable to individualized decision-making, the FH in both groups was comparable (161.5 cm in treated, 161.0 cm in untreated girls with iCPP), although the onset of menarche was 2.5 years earlier among untreated girls. BW-adjusted dosing suppressed peak luteinizing hormone (LH) below 4.5 IU/L in 95% of children; however, bone age further advanced during therapy in 38% of patients. Predicting factors revealed by multivariable regression were bone age at diagnosis, BMI SDS at diagnosis, LH basal, age at start and cessation of treatment, predicted adult height and target height. (R2 = 0.72).
Children with nCPP had worse FH outcome compared to iCPP despite similar CPP onset and therapeutic characteristics. Treatment by GnRHa using BW-adjusted dosing was effective in delaying menarche onset and reaching target height in girls with iCPP. Multiple factors affecting FH outcome indicated individualized decision-making regarding therapeutic intervention remains challenging. In the treated patients, among the factors that can be influenced, height at treatment cessation most significantly influenced the outcome.
Proopiomelanocortin (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. A novel MC4R agonist, setmelanotide, has shown promising results regarding weight loss in patients with POMC deficiency. A systematic review on previously published clinical and genetic characteristics of patients with POMC deficiency and additional data obtained from two unrelated patients in our care was performed. A 25-year-old male patient, partly previously reported, was remarkable for childhood developed type 1 diabetes (T1D), transient growth hormone deficiency, and delayed puberty. The second case is a girl with an unusual presentation with central hypothyroidism and normal pigmentation of skin and hair. Of all evaluated cases, only 50% of patients had characteristic red hair, fair skin, and eye phenotype. Central hypothyroidism was reported in 36% of patients; furthermore, scarce adolescent data indicate possible growth axis dysbalance and central hypogonadism. T1D was unexpectedly prevalent in POMC deficiency, reported in 14% of patients, which could be an underestimation. POMC deficiency reveals to be a syndrome with several endocrinological abnormalities, some of which may become apparent with time. Apart from timely diagnosis, careful clinical follow-up of patients through childhood and adolescence for possible additional disease manifestations is warranted.
BackgroundOverweight/obesity in children is a worldwide public health problem. Together with hypercholesterolaemia they are associated with early atherosclerotic complications.ObjectivesIn this ...study, we aimed to investigate the anthropometric characteristics and total cholesterol (TC) levels in a population of 5-year-old children, to determine trends in the prevalence of overweight/obesity and hypercholesterolaemia in 5-year-old children over a period of 8 years (2001–2009) and to assess the impact of modified national nutritional guidelines for kindergartens implemented in 2005.DesignCross-sectional studies of overweight/obesity prevalence in the years 2001, 2003–2005 and 2009, and hypercholesterolaemia in years 2001 and 2009, in 5-year-old children.SubjectsAltogether, 12 832 (6308 girls/6524 boys) children were included.MethodsOverweight/obesity was defined by IOTF criteria. Hypercholesterolaemia was defined by TC level >5 mmol/l. Multivariable logistic regression models were used.ResultsNo correlation between BMI values and TC levels was found. Overweight and obesity prevalence were stabilised from 2001 to 2009 (odds ratio (OR) (95% CI): 1.13 (0.99–1.3) and 1.13 (0.89–1.42) respectively). Girls were more frequently overweight/obese than boys (OR (95% CI): 0.71 (0.65–0.79) and 0.75 (0.64–0.89) respectively). Prevalence of hypercholesterolaemia significantly decreased from 2001 to 2009 (OR (95% CI): 0.47 (0.41–0.55)). It was less frequent in boys than in girls (OR (95% CI): O.7 (0.61–0.8)).ConclusionsThis is the first study to describe a negative trend in the prevalence of hypercholesterolaemia in pre-pubertal children. In addition, the prevalence of overweight/obesity in these children has been stabilised. Nationwide changes in public health policies could have influenced these observations.
PDF
