Persistent hypoglycaemia in newborns and infants is most commonly caused by congenital hyperinsulinism (CHI). Most CHI studies report outcomes in children from both consanguineous and ...non-consanguineous families which can affect the phenotype-genotype analysis. The aim of this study was to analyze characteristics of patients with CHI in 21 non-consanguineous families from Serbia. This retrospective cohort study included a total of 21 patients with CHI treated in the Mother and Child Healthcare Institute of Serbia during the past 20 years. The prevalence of macrosomia at birth was very low in our cohort (4.8%). Median age at presentation was 6 days, with seizures as the presenting symptom in 76% of patients. Only four patients (19%) were diazoxide unresponsive, and eventually underwent pancreatectomy. Genetic testing was performed in 15 patients and genetic diagnosis was confirmed in 60%, with all patients being heterozygous for detected mutations. The
ABCC8
gene mutations were detected in 55.6%,
GLUD1
in three patients (33.3%) with HIHA syndrome and one patient had
HNF4A
gene mutation and unusual prolonged hyperglycaemia lasting 6 days after diazoxide cessation. Neurodevelopmental deficits persisted in 33% of patients.
Conclusion
: This is the first study regarding CHI patients in Serbia. It suggests that in countries with low consanguinity rate, majority of CHI patients are diazoxide responsive. The most common mutations were heterozygous
ABCC8
, followed by
GLUD1
and
HNF4A
mutations, suggesting the potential benefit of population-tailored genetic analysis approach, targeting the mutations causing CHI via dominant inheritance model in regions with low consanguinity rates.
What is Known:
• Persistent hypoglycaemia during infancy and early childhood is most commonly caused by congenital hyperinsulinism (CHI).
• Consanguinity is a very important factor regarding the genetics and phenotype of CHI, increasing the risk of autosomal recessive genetic disorders, including the severe, diazoxide-unresponsive forms caused by recessive inactivating mutations in ABCC8 and KCNJ11.
What is New:
• Results of the present study which included CHI patients from 21 non-consanguineous families suggest that in countries with low consanguinity rates, majority of CHI patients can be diazoxide responsive, with most common mutations being heterozygous ABCC8, followed by GLUD1 and HNF4A mutations.
• Unusually prolonged hyperglycaemic reaction to diazoxide treatment in a patient with HNF4A mutation was also described in the present study.
This case report describes a patient harboring TARS2 mutations where chronic kidney disease stands out as the predominant clinical feature. The distinct manifestation observed in this case ...underscores the importance of continual exploration and documentation of diverse clinical presentations associated with TARS2 mutations, contributing to an enriched comprehension of the spectrum of effects linked to this genetic variation
Introduction. Mutations in TMEM38B gene, which encodes the endoplasmatic reticulum membrane trimeric intracellular cation channel (TRIC) type B, cause osteogenesis imperfecta type XIV. So far there ...have been only four different pathogenic variants reported in TMEM38B. Clinical features of osteogenesis imperfecta type XIV described in scarce reports include osteopenia, femoral bowing, low trauma fractures, scoliosis, muscular hypotonia and cardiac pathology.
Case report. A 2-month-old male infant was referred to a clinical geneticist office due to bone deformities. The shortening of the limbs was observed during the prenatal ultrasound examination in seventh month of pregnancy. Prenatal cytogenetic analysis was performed from a fetal blood sample and showed normal findings. Neither fetal fractures were observed prenatally, nor any occurred during vaginal labor. During the first clinical exam by the clinical geneticist, discrete rhizomelia and bluish sclerae were observed. Due to the suspicion of skeletal dysplasia, indication for genetic analysis was established. Next generation sequencing panel for skeletal dysplasia showed homozygous deletion of exons 1 and 2 in the TMEM38B gene, confirming osteogenesis imperfecta type XIV. At the follow-up visit performed at 12 months of age, no fractures were reported. Several skeletal deformities were observable: discrete frontal bossing, rhizomelic upper extremities, slightly bowed thighs and shins. The infant achieved normal psychomotor development. A radiographic examination showed bowing of long bones of the lower extremities, without significant osteopenia.
Conclusion. Absence of early fractures is rare in osteogenesis imperfecta type XIV. Relatively mild clinical features of our patient therefore contribute to the understanding of the phenotype of osteogenesis imperfecta type XIV and its relation to the genotype.
Introduction. Patients affected with Allan-Herndon-Dudley syndrome (AHDS) have a deficiency of monocarboxylate transporter 8 (MCT8), a protein primarily responsible for the transport of ...triiodothyronine (T3) into the brain. This X-linked disorder affects almost exclusively males with clinical presentation encompassing developmental delay, axial hypotonia, dystonia, poor head control, quadriplegia and absence of speech. Case reports. Patient 1 is a male child referred to a hospital investigation at 11 months due to severe developmental delay and elevated blood ammonia level (163 mcmol/L). Hypotonia and dystonic movements were noted at admission, with facial dysmorphic features. Laboratory findings revealed increased blood lactate (17.2 mmol/L), alanine (533 mcmol/L) and ammonia (391 mcmol/L) concentrations. Serum creatine-kinase levels showed substantial increase over the course of hospitalization up to 6,855 IU/L. Clinical exome sequencing detected a novel hemizygous frameshift insertion c.1456insC in gene SLC16A2, predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. Segregation genetic testing of the family members revealed that mother, maternal uncle and maternal grandmother carry the same mutation in SLC16A2. The boy`s mother experienced learning difficulties through childhood while maternal uncle is severely affected by AHDS. Patient 2 is a boy referred to clinical geneticist due to severe psychomotor delay of unknown etiology. Moderate serum lactate elevation was the only laboratory abnormality during initial investigations. Diagnosis of AHDS was established by clinical exome sequencing, and subsequent hormonal evaluation revealed increased triiodothyronine (T3) level which corresponds well to genetic diagnosis. Conclusion. Presence of lactic acidosis and/or hyperammonemia in children with severe developmental delay is not specific for inborn disorders of energy production, such as mitochondrial disease. Clinicians should consider thyroid hormones profiling in cases of unexplained severe developmental delay in male children, especially if associated with axial hypotonia and dystonic movements.
This study delves into the diagnostic yield of whole-exome sequencing (WES) in pediatric patients presenting with developmental delay/intellectual disability (DD/ID), while also exploring the utility ...of Reverse Phenotyping (RP) in refining diagnoses. A cohort of 100 pediatric patients underwent WES, yielding a diagnosis in 66% of cases. Notably, RP played a significant role in cases with negative prior genetic testing, underscoring its significance in complex diagnostic scenarios. The study revealed a spectrum of genetic conditions contributing to DD/ID, illustrating the heterogeneity of etiological factors. Despite challenges, WES demonstrated effectiveness, particularly in cases with metabolic abnormalities. Reverse phenotyping was indicated in half of the patients with positive WES findings. Neural network models exhibited moderate-to-exceptional predictive abilities for aiding in patient selection for WES and RP. These findings emphasize the importance of employing comprehensive genetic approaches and RP in unraveling the genetic underpinnings of DD/ID, thereby facilitating personalized management and genetic counseling for affected individuals and families. This research contributes insights into the genetic landscape of DD/ID, enhancing our understanding and guiding clinical practice in this particular field of clinical genetics.
Introduction/Objective. Acute disseminated encephalomyelitis (ADEM) is the most common demyelinating disease of the central nervous system in pediatric patients. We aimed to evaluate the clinical ...profile of children with ADEM and to discern prognostic factors for disease outcome. Methods. A 20-year retrospective?prospective study was conducted in a cohort with the diagnosis of ADEM. Results. The study included 36 patients, with range of follow-up period of 6?120 months (median of 26 months). Prior infection was reported in 72.2% of the patients. In the clinical presentation of the disease, motor deficit was most common (81.1%), followed by ataxia (77.8%). More than a third of patients had back and limb pain or abdominal visceral pain, which highly correlated with MRI findings of myelitis. Abnormal brain CT findings were evident in 22.2% of the patients, and this was associated with higher Expanded Disability Status Scale (EDSS) and quicker progression of the disease. Median EDSS was 0 at the most recent follow-up visit, in all the patients. EDSS 0?2.5 was verified in 29 (80.6%) of the patients, while three (8.3%) patients scored 7?9.5 at the last visit. Two patients had a lethal outcome. Conclusions. ADEM is a serious disease in pediatric patients, but with a good prognosis, which is illustrated by the fact that 80.6% of our patients had a complete or almost complete recovery.
Patients with Angelman syndrome (AS) are affected by severe intellectual disability with absence of speech, distinctive dysmorphic craniofacial features, ataxia and a characteristic behavioral ...phenotype. AS is caused by the lack of expression in neurons of the UBE3A gene, which is located in the 15q11.2-q13 imprinted region. Functional loss of UBE3A is due to 15q11.2-q13 deletion, mutations in the UBE3A gene, paternal uniparental disomy and genomic imprinting defects.
We report here two patients with clinical features of AS referred to our hospital for clinical follow-up and genetic diagnosis. Methylation Specific-Multiplex Ligation-Dependent Probe Amplification (MS-MLPA) of the 15q11.2-q13 region was carried out in our laboratory as the first diagnostic tool detecting two novel UBE3A intragenic deletions. Subsequently, the MLPA P336-A2 kit was used to confirm and determine the size of the UBE3A deletion in the two patients. A review of the clinical features of previously reported patients with whole UBE3A gene or partial intragenic deletions is presented here together with these two new patients.
Although rare, UBE3A intragenic deletions may represent a small fraction of AS patients without a genetic diagnosis. Testing for UBE3A intragenic exonic deletions should be performed in those AS patients with a normal methylation pattern and no mutations in the UBE3A gene.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Kaposiform haemangioendothelioma (KHE) is a rare, locally invasive vascular tumour that is commonly associated with the Kasabach-Merritt phenomenon (KMP). A case of a five-month-old female infant ...admitted for dyspnoea, stridor, and skin haematoma is presented. Computerised tomography of the chest showed a tumour mass occupying mediastinum and most of the left hemithorax, while laboratory analysis revealed a thrombocytopaenia and a consumption coagulopathy. Histology of tumour biopsy was characteristic of KHE with a component of tufted angioma. Corticosteroid treatment initially induced a reduction in tumour size, but progression occurred four weeks later and led to a fatal outcome despite additional chemotherapy. After a literature search, we found only 18 cases of mediastinal KHE published so far, with 21 % fatality rate. In the present case several risk factors for adverse outcome were present: onset of disease in early infancy, a large volume of the tumour, mediastinal location, KMP, and partial response to available therapy.
Homelessness is a problem with social, medical, economic, political and other implications. Despite a large number of studies, reports about health-related quality of life (HRQoL) of homeless persons ...remain sparse. There is a summary of consistent evidence that homeless people have higher prevalence of chronic disease (mental and somatic) than general population. The aim of this study was to assess HRQoL and depression in homeless persons in Belgrade, to describe their sociodemographic factors and health status (the presence of chronic mental and somatic diseases and addiction disorders) and analyse impact of sociodemographic factors and health status to HRQoL and depression of homeless persons.
The study was conducted in the Shelter for Adult and Elderly Persons in Belgrade, from January 1 to January 31, 2012. A set of questionnaires used in survey included Serbian translation of SF-36 questionnaire, Serbian translation of Beck Depression Inventory-II (BDI-II) and sociodemographic questionnaire. Statistical analysis was performed by descriptive and analytic methods.
Our study sample consisted of 104 adult participants. The majority of them were male (74%) and the mean age in the sample was 48.2 +/- 13.0 years. We have found that 35.6% participants had lifetime diagnosis of psychiatric disorder, most frequently depression (lifetime prevalence of 15.4% in the study group). The history of suicide attempts was registered in 28 (26.9%) participants. Lifetime illicit drugs use was reported by 12.5%, daily smoking by 82.7% and daily alcohol consumption by 8.7% of the participants. Most common somatic chronic diseases were cardiovascular while chronic lung diseases were the second most frequent. Single chronic disaese was present in 33 (31.7%) of the participants and comorbidity of 2 chronic diseases was present in 20 of them. A statistically significant difference between participants HRQoL SF-36 domain scores and norms of general population was found only for role physical domain (lower in homeless, p < 0.001). ANOVA showed no statistically significant difference in SF-36 HRQoL domain and composite scores between different age groups, nor did marital status, education level, length of homelessness, alcohol use or smoking significantly affect the HRQoL. The mean BDI-II score in the studied population was 19.1 +/- 11.6. Severe depression was registered in 20.2% of the participants, moderate in 23.1%, mild in 19.2% and minimal in 37.5%. A highly significant negative correlation was verified between BDI-II and all domains and composite scores of SF-36 (p < 0.001).
Measures for prevention of homelessness should include: foundation of national registry of homeless persons, development of systemic multisectorial cooperation and special psychosocial intervention strategies. In homeless population, health care measures should be focused on prevention and treatment of mental health disorders and chronic somatic diseases.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
PDF
