Precocious puberty in a girl with 3-methylglutaconic aciduria type 1 (3-MGA-I) due to a novel AUH gene mutation

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

Attachment in close relationships and glycemic outcomes in children with type 1 diabetes

Background: Our aim was to determine whether child attachment to parents, parent attachment style, and morning cortisol levels were related to diabetes outcomes measured by average glycated hemoglobin (HbA1c), HbA1c variability over 4 years and time in range (TIR) in children with type 1 diabetes (T1D). Research design and methods: 101 children with T1D and one of their parents were assessed at baseline for child attachment (Child Attachment InterviewCAI) and parent attachment (Relationship Structures QuestionnaireECR-RS). Serum samples were collected for cortisol measurements before the interviews. HbA1c levels were measured during a 4-year follow-up period at regular 3-monthly visits, and data for TIR were exported from blood glucose measuring devices. Multivariate linear regression models were constructed to identify independent predictors of glycemic outcomes. Results: More girls than boys exhibited secure attachment to their mothers. The results of the regression models showed that securely attached girls (CAI) had higher average HbA1c than did insecurely attached girls (B = -0.64, p = 0.03). In boys, the more insecure the parent\u27s attachment style, the worse the child\u27s glycemic outcome: the higher the average Hb1Ac (B = 0.51, p = 0.005), the higher the HbA1c variability (B = 0.017, p = 0.011), and the lower the TIR (B = -8.543, p = 0.002). Conclusions: Attachment in close relationships is associated with glycemic outcomes in children with T1D, and we observed significant differences between sexes. A sex- and attachment-specific approach is recommended when treating children with less favorable glycemic outcomes. Special attention and tailored support should be offered to securely attached girls in transferring responsibility for diabetes care and at least to male children of insecurely attached parents to prevent suboptimal glycemic control. Further studies in larger samples and more daily cortisol measurements may help us better understand the links between stress response, attachment and T1D

Newborn Screening in Slovenia / Presejanje Novorojencev V Sloveniji

Uvod. Presejanje novorojencev v Sloveniji se je začelo leta 1979 s presejanjem za fenilketonurijo (PKU). Leta 1981 je bil v program presejanja dodan še kongenitalni hipotireoidizem (CH). Cilj te raziskave je analiza podatkov presejanja novorojencev v Sloveniji v obdobju med letoma 1993 in 2012 za PKU ter med letoma 1991 in 2012 za CH. Metode. Vzorci krvi so bili odvzeti petim novorojencem med tretjim in petim dnem življenja. Pri presejanju za PKU se uporablja fluorometrična metoda, presejanje za CH pa poteka z metodo DELFIA. Rezultati. Od leta 1993 do leta 2012 je bil presejalni test za PKU izveden pri 358.831 novorojencih. Pri 57 otrocih je bil PKU potrjen. Pri 427.396 novorojencih med letoma 1991 in 2012 je bil izveden presejalni test za CH. Pri 184 otrocih je bil CH potrjen. V navedenih obdobjih je bila incidenca PKU 1:6769 in incidenca CH 1:2323. Zaključki. Uspešna implementacija presejanja novorojencev za PKU in CH je imela pomembno vlogo pri preprečevanju resnih zapletov pri obolelih otrocih. Smiselno bi bilo v program presejanja vključiti nove metabolne bolezni

Expanded newborn screening program in Slovenia using tandem mass spectrometry and confirmatory next generation sequencing genetic testing

In the last two decades, the introduction of tandem mass spectrometry in clinical laboratories has enabled simultaneous testing of numerous acylcarnitines and amino acids from dried blood spots for detecting many aminoacidopathies, organic acidurias and fatty acid oxidation disorders. The expanded newborn screening was introduced in Slovenia in September 2018. Seventeen metabolic diseases have been added to the pre-existing screening panel for congenital hypothyroidism and phenylketonuria, and the newborn screening program was substantially reorganized and upgraded

Clinical and genetic characteristics of two patients with tyrosinemia type 1 in Slovenia – a novel fumarylacetoacetate hydrolase (FAH) intronic disease-causing variant

Tyrosinemia type 1 (HT1) is an inborn error of tyrosine catabolism that leads to severe liver, kidney, and neurological dysfunction. Newborn screening (NBS) can enable a timely diagnosis and early initiation of treatment. We presented the follow up of the only two Slovenian patients diagnosed with HT1. Metabolic control was monitored by measuring tyrosine, phenylalanine and succinylacetone from dried blood spots (DBSs). Retrograde screening of HT1 was performed from DBSs taken at birth using tandem mass spectrometry. First patient was diagnosed at the age of 6 months in the asymptomatic phase due to an abnormal liver echogenicity, the other presented at 2.5 months with an acute liver failure and needed a liver transplantation. The first was a compound heterozygote for a novel FAH intronic variant c.607-21A>G and c.192G>T whereas the second was homozygous for c.192G>T. At the non-transplanted patient, 66% of tyrosine and 79% of phenylalanine measurements were in strict reference ranges of 200–400 μmol/L and >30 μmol/L, respectively, which resulted in a favorable cognitive outcome at 3.6 years. On retrograde screening, both patients had elevated SA levelson the other hand, tyrosine was elevated only at one. We showed that non-coding regions should be analyzed when clinical and biochemical markers are characteristic of HT1. DBSs represent a convenient sample type for frequent amino acid monitoring. Retrograde diagnosis of HT1 was possible after more than three years of birth with SA as a primary marker, complemented by tyrosine