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#46
25.02.2023, 19:06
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....patients with KH without metabolic and hormonal biomarkers are often classified within idiopatic ketotic hypoglycemia (IKH). IKH has been mostly considered as a non-pathological condition of children with a fasting tolerance at the lower tail of the Gaussian normal distribution until school age (83). However, some children continue to present IKH until adulthood. Pathological KH has been defined as recurrent episodes with blood glucose < 70 mg/dl (3.9 mmol/L) and betahydroxybutyrate ≥ 1.0 mmol/L, without any trigger of fasting or infections. Pathological KH may be due to underlying diseases, e.g. GSDs, defective MCT and genetic syndromes or to novel diseases that can be identified by whole exome sequencing (WES)...
By use of trio exome sequencing in patients with IKH, researchers have identified variants also in SLC16A1 (MCT1), NCOR1, IGF2BP1, SGLT2 and NEK11 as potential novel causes of unexplained KH. 
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#47
25.02.2023, 20:28
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Цитата:
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#48
26.02.2023, 08:50
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Таеим обрпзом, неаедомо, какие исследования проводили. Выше дана ссылка
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#51
26.02.2023, 18:08
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Мальчику проведён полноэкзомный сиквенс методом NGS - это действительно на сегодня достаточно убедительные данные о том, что специфических мутаций не выявлено
У девочки приведены данные по анализу аминокислот
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#53
26.02.2023, 19:23
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преимущества и недостатки тех или иных методик в выявлении новых ген. поломок, связанных с гипогликемией, и почему успех у трио - папа-мама-ребенок:
WES has a higher diagnostic yield. WES detects all variants within the entire protein-coding region (∼20,000 genes), representing less than 2% of the genome but containing the ∼ 85% of known disease-causing variants. WES is suitable for novel gene discovery in idiopathic conditions. However, non-coding and structural variants cannot be captured, and the gene coverage may be variable. Therefore, the detection of mutations in deep intronic regions may be missed by the use of gene panels or WES, or if a detected mutation was considered as a nonpathogenic variant. Whole-genome sequencing (WGS) captures variants from the entire genome. Besides revealing the ∼98% of the non-coding regions, it provides a better coverage and analysis of the coding regions. Indeed, WGS revealed large deletions in genes associated to some IEM, not detected by WES. Nevertheless, reliable tools to interpret non-coding variants are still not available, and cost and turnaround time are high. However, the buildup of WES and WGS data in the human population and the systematic use of trio sequencing will possibly increase the diagnostic yield in unexplained conditions (79). Though, as WES and WGS lean on short-read sequencing, there are genomic regions still difficult to sequence such as tandem-repeat expansion, large deletions and insertions, and complex chromosomal structural abnormalities. In those cases, long-read sequencing technologies could unveil such rare variations. Recent studies about the application of long-read sequencing to pathogenic variants in rare diseases not detected by conventional NGS techniques gave promising results... --- Front Endocrinol (Lausanne). 2022; 13: 826167. Hypoglycaemia Metabolic Gene Panel Testing
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#54
26.02.2023, 19:34
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Цитата:
hypoglycemia attributed to poor oral intake or illness [3, 9, 39]. In a series of 62 children with KH, 29% had, however, no history of a precipitating event that could explain the hypoglycemia [40]. To the authors’ experience, increased physical activity and poor food intake the day before can be identified in a higher number of patients after detailed evaluation at the time of a KH event. Remission of IKH is classically thought to occur between 6–7 years of age when children have increased their muscle mass and decreased their glucose requirement per unit of body mass [40, 41]. In some patients, episodes of KH may persist past puberty into adulthood, and family investigations may reveal parents with a history of KH... Children with KH may exhibit a wide range of symptoms and signs. Younger children cannot be relied upon to accurately recognize and communicate symptoms of hypoglycemia [13, 37, 38, 43,44,45]...Episodes frequently occur in the morning after an overnight fast (10–12 h). The presence of neuroglycopenic symptoms despite the brain-protective hyperketonemia may suggest a ketone utilization or ketone transport defect in these patients. What makes KH particularly complex is that some of the symptoms, such as muscle cramps, headache and abdominal pain, may result from either hypoglycemia or hyperketonemia. Some children with IKH are small and thin for their age, with minimal fat deposits or muscle development [41]. Such children have little to no tolerance for fasting and often display poor eating habits. The poor appetite may be caused by hyperketonemia, inducing a vicious cycle provoking further KH.
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#55
26.02.2023, 19:40
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и по генетике - не у всех обнаруживаются ген. дефекты - описание случая у одного ребенка, но отсутствие у его близнеца - говорит о том, что проблема сложнее, чем одна мутация = одна болезнь:
A number of children with pathological KH remains unexplained despite trio exome sequencing [42]. Pathological KH may well represent a disease entity with several different unidentified monogenetic, digenic, polygenetic, or epigenetic causes [12, 30]. A case report with KH in one, but not the other homozygotic twin illustrates the complexity of KH [55].
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