Seizures and diagnostic difficulties in hyperinsulinism-hyperammonemia syndrome

Aka, Sibel; Alanay, Yasemin; Boodhansingh, Kara E.; Stanley, Charles A.; Semiz, Serap

doi:10.24953/turkjped.2016.05.014

Cited by 5 publications

(3 citation statements)

References 7 publications

(9 reference statements)

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“…It is also interesting to outline that almost half of the proteins that are differentially expressed in EPM1‐derived organoids and enriched in radial glial cells are involved in different types of human epilepsies. For instance, Collagen COL11A1 mutated in the Stickler syndrome, caused by mutations in COL2A1 or COL11A1, is associated with epileptic phenotypes (Savasta et al , ; Zhou et al , ); IFITM3 (interferon‐induced transmembrane protein 3) has been identified among genes that are target of epilepsy‐associated miRNA in animal models and human tissues (Cava et al , ); heterozygous mutation in GLUD1 gene has been reported in patients affected by hyperinsulinism, commonly associated with epileptic seizures (Aka et al , ); RRAS (Guo et al , ) and MGST1 (Shang et al , ; Ercegovac et al , ) are associated with epilepsy risk.…”

Section: Discussionmentioning

confidence: 99%

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

et al. 2020

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Progressive myoclonus epilepsy (PME) of Unverricht-Lundborg type (EPM1) is an autosomal recessive neurodegenerative disorder with the highest incidence of PME worldwide. Mutations in the gene encoding cystatin B (CSTB) are the primary genetic cause of EPM1. Here, we investigate the role of CSTB during neurogenesis in vivo in the developing mouse brain and in vitro in human cerebral organoids (hCOs) derived from EPM1 patients. We find that CSTB (but not one of its pathological variants) is secreted into the mouse cerebral spinal fluid and the conditioned media from hCOs. In embryonic mouse brain, we find that functional CSTB influences progenitors' proliferation and modulates neuronal distribution by attracting interneurons to the site of secretion via cell-non-autonomous mechanisms. Similarly, in patient-derived hCOs, low levels of functional CSTB result in an alteration of progenitor's proliferation, premature differentiation, and changes in interneurons migration. Secretion and extracellular matrix organization are the biological processes particularly affected as suggested by a proteomic analysis in patients' hCOs. Overall, our study sheds new light on the cellular mechanisms underlying the development of EPM1.

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Section: Discussionmentioning

confidence: 99%

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

et al. 2020

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“… 7 This can lead to developmental delays and, if it remains undiagnosed, can lead to permanent neurologic damage. 7 , 8 Patients with HI/HA syndrome are usually responsive to diazoxide, which is an ATP-sensitive potassium (KATP) channel agonist. 1 , 5 , 9 , 10 There has been a report of variable phenotypes of this condition ranging from delayed presentation to spontaneous resolution of hypoglycemia but no report of T2DM developing in a patient with GLUD1 alteration.…”

Section: Discussionmentioning

confidence: 99%

A Very Rare Case of Diabetes Mellitus Occurring in a Patient With Hyperinsulinism Hyperammonemia Syndrome

Komal¹,

Olajide²

2023

AACE Clinical Case Reports

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“…It is caused due to an activating mutation in the GLUD1 gene, which is located on chromosome 10q23.3 (contains 13 exons) and encodes the intra-mitochondrial matrix enzyme glutamate dehydrogenase (GDH). Approximately 70% of these children have de novo mutation and 30% present with autosomal dominant inheritance ( 1 , 2 ).…”

Section: Introductionmentioning

confidence: 99%

Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1

Aftab

Gubaeva

Houghton

et al. 2023

Endocrine Connections

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Background: Hyperinsulinism/hyperammonemia (HI/HA) syndrome is the second most common type of congenital hyperinsulinism caused by an activating GLUD1 mutation. Objective: The aim of this study was to determine the clinical profile and long-term neurological outcomes in children with HI/HA syndrome. Method: Retrospective review of patients with GLUD1 mutation, treated at two centers in the UK and Russia, over a 15-year period. Different risk factors for neuro-developmental disorders were analyzed by Mann-Whitney U test and Fisher exact p. Results: We identified 25 cases with GLUD1 mutations (12 males). Median age of presentation was 7 months (12 hours-18 months). Hypoglycaemic seizures were the presenting feature in 24 (96%) cases. 24 cases responded to diazoxide and protein restriction whilst one patient underwent partial pancreatectomy. In total, 13 cases (52%) developed neurodevelopmental manifestations. Epilepsy (n=9/25, 36%), learning difficulties (n=8/25, 32%) and speech delay (n=8/25, 32%) were the most common neurological manifestation. Median age of presentation for epilepsy was 12 months with generalized tonic-clonic seizures being the most common (n=4/9, 44.4%) followed by absence seizures (n=3/9, 33.3%). Early age of presentation (p=0.02), diazoxide dose (p=0.04), and a mutation in exon 11 or 12 (p=0.01) was associated with neurological disorder. Conclusion: HI/HA syndrome is associated with wide spectrum of neurological disorders. These neurological manifestations were more frequent in cases with mutations affecting the GTP-binding site of GLUD1 in our cohort.

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Seizures and diagnostic difficulties in hyperinsulinism-hyperammonemia syndrome

Cited by 5 publications

References 7 publications

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

Cystatin B is essential for proliferation and interneuron migration in individuals with EPM 1 epilepsy

A Very Rare Case of Diabetes Mellitus Occurring in a Patient With Hyperinsulinism Hyperammonemia Syndrome

Spectrum of neuro-developmental disorders in children with congenital hyperinsulinism due to activating mutations in GLUD1

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