Sirolimus precipitating diabetes mellitus in a patient with congenital hyperinsulinaemic hypoglycaemia due to autosomal dominant ABCC8 mutation

2017 ◽  
Vol 30 (11) ◽  
Author(s):  
Antonia Dastamani ◽  
Maria Güemes ◽  
Joanna Walker ◽  
Pratik Shah ◽  
Khalid Hussain
Keyword(s):  
Diabetes Mellitus ◽  
Mtor Inhibitor ◽  
Autosomal Dominant ◽  
Congenital Hyperinsulinism ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Case Presentation

AbstractBackground:Sirolimus (mTOR inhibitor) is proven to be effective in children with congenital hyperinsulinism (CHI). Studies in animals suggest that sirolimus may have diabetogenic actions. However, its role in precipitating diabetes mellitus (DM) in children with CHI has not been reported.Case presentation:A 16-year-old female with CHI due to a dominantConclusions:Patients with dominant

Clinical presentation and treatment response to diazoxide in two siblings with congenital hyperinsulinism as a result of a novel compound heterozygous ABCC8 missense mutation

2017 ◽  
Vol 30 (4) ◽  
Author(s):  
Sonya Galcheva ◽  
Violeta Iotova ◽  
Sian Ellard ◽  
Sarah E. Flanagan ◽  
Irina Halvadzhiyan ◽  
...  
Keyword(s):  
Clinical Presentation ◽  
Index Patient ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Compound Heterozygosity ◽  
Clinical Heterogeneity ◽  
Intravenous Glucose ◽  
Hyperinsulinaemic Hypoglycaemia ◽  
Case Presentation ◽  
Compound Heterozygotes

AbstractBackground:Congenital hyperinsulinism (CHI) can present with considerable clinical heterogeneity which may be due to differences in the underlying genetic etiology. We present two siblings with hyperinsulinaemic hypoglycaemia (HH) and marked clinical heterogeneity caused by compound heterozygosity for the same two novelCase presentation:The index patient is a 3-year-old boy with hypoglycaemic episodes presenting on the first day of life. HH was diagnosed and treatment with intravenous glucose and diazoxide was initiated. Currently he has normal physical and neurological development, with occasional hypoglycaemic episodes detected following continuous fasting on treatment with diazoxide. The first-born 8-year-old sibling experienced severe postnatal hypoglycaemia, generalised seizures and severe brain damage despite diazoxide treatment. The latter was stopped at 6-months of age with no further registered hypoglycaemia. Genetic testing showed that both children were compound heterozygotes for two novelConclusions:These

Sirolimus in the treatment of three infants with diffuse congenital hyperinsulinism

2017 ◽  
Vol 30 (9) ◽  
Author(s):  
Rana Al-Balwi ◽  
Mohsen Al-Atawi ◽  
Ahlam Al-Otaibi ◽  
Omar Babiker ◽  
Angham Al-Mutair
Keyword(s):  
Genetic Testing ◽  
Mtor Inhibitor ◽  
Total Pancreatectomy ◽  
Mammalian Target Of Rapamycin ◽  
Therapeutic Strategies ◽  
Congenital Hyperinsulinism ◽  
Diffuse Type ◽  
Homozygous State ◽  
Case Presentation ◽  
Homozygous Mutations

AbstractBackground:Congenital hyperinsulinism (CHI) is a major cause of persistent hypoglycemia and brain damage. Therapeutic strategies to avoid near total pancreatectomy in patients who are unresponsive to maximum doses of diazoxide and octreotide remain to be identified, although sirolimus, a mammalian target of rapamycin (mTOR) inhibitor, has been used successfully to treat diffuse type CHI.Case presentation:We used sirolimus to treat three infants with diffuse CHI. Diagnosis was confirmed clinically, biochemically and by genetic testing. Homozygous mutations inConclusions:We conclude that sirolimus is less effective in the treatment of diffuse CHI in patients with severe mutations in the homozygous state compared with those with the mutations in the heterozygous.

Myotone Dystrophie Typ 2/proximale myotone Myopathie

2004 ◽  
Vol 23 (08) ◽  
pp. 447-453
Author(s):  
T. Müller ◽  
T. Wieser
Keyword(s):  
Diabetes Mellitus ◽  
Autosomal Dominant ◽  
Kognitive Defizite ◽  
Kausale Therapie ◽  
Rna Foci ◽  
Myotone Dystrophie ◽  
Proximale Myotone Myopathie

ZusammenfassungDie myotone Dystrophie Typ 2 ist eine autosomal-dominant vererbte, multisystemische Erkrankung. Klinische Hauptmerkmale sind proximale Paresen und Atrophien, Myotonie und Katarakt. Eine Vielzahl assoziierter Symptome in wechselnder Ausprägung ist beschrieben worden, darunter Schmerzen der Muskulatur, Erhöhung der CK und der Leberwerte, Glukose-Intoleranz bzw. Diabetes mellitus und andere endokrine Auffälligkeiten, Hörstörungen, kognitive Defizite, Veränderungen der weißen Substanz in der MRT und möglicherweise Herzmuskelbeteiligung. Im Vergleich mit der myotonen Dystrophie Typ 1 (Curschmann-Steinert-Dystrophie) ist der Verlauf deutlich milder. Auslöser ist eine Mutation im ZNF9 Gen auf Chromosom 3. Die Funktion dieses Gens und der Pathomechanismus, der zu dem komplexen Phänotyp dieser Erkrankung führt, ist nicht bekannt. Spekuliert wird, dass toxische RNA-Foci über Beeinflussung der Translation negativ auf ZNF9 und benachbarte Gene wirken. Die Diagnose kann molekulargenetisch durch Nachweis der Mutation gestellt werden. Eine kausale Therapie steht nicht zur Verfügung, neben der Operation der Katarakt steht Physiobzw. Ergotherpie im Vordergrund.

Efficacy and safety of denosumab treatment in a prepubertal patient with cherubism

2020 ◽  
Vol 33 (7) ◽  
pp. 963-966
Author(s):  
Haruka Kawamura ◽  
Satoshi Watanabe ◽  
Takashi I ◽  
Izumi Asahina ◽  
Hiroyuki Moriuchi ◽  
...  
Keyword(s):  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Giant Cells ◽  
Efficacy And Safety ◽  
Autosomal Dominant Disorder ◽  
Osteolytic Lesions ◽  
Case Presentation ◽  
Childhood Growth ◽  
Receptor Activator ◽  
Denosumab Treatment

AbstractBackgroundDenosumab is an inhibitor of receptor activator of nuclear factor kappa-B ligand, which strongly suppresses osteoclasts. Cherubism is a rare autosomal dominant disorder characterized by symmetrical swelling of the jaws, in which the bone is replaced by a fibrous granuloma containing osteoclast-like giant cells.Case presentationWe report the efficacy and safety of denosumab treatment in a prepubertal boy with progressive cherubism. The treatment consisting of eight subcutaneous denosumab injections (120 mg/dose) in 6 months not only suppressed the expansion of the osteolytic lesions but also dramatically ossified them. However, a transiently decreased growth rate and rebounded asymptomatic hypercalcemia were associated with the treatment.ConclusionsThe present case demonstrated the therapeutic potential of denosumab for treatment of cherubism, although adverse effects, especially those on childhood growth, remain obscure. Further studies are needed to establish a safe and effective protocol for denosumab treatment of children.

Autosomal Dominant Frontotemporal Lobar Degeneration in a Filipino Family with Progranulin Mutation

2021 ◽  
pp. 1-8
Author(s):  
Jacqueline Dominguez ◽  
Arlene Ng ◽  
Jeryl Yu ◽  
Anne Cristine Guevarra ◽  
Maria Luisa Daroy ◽  
...  
Keyword(s):  
Frontotemporal Lobar Degeneration ◽  
White Matter Hyperintensities ◽  
Autosomal Dominant ◽  
The Philippines ◽  
Vascular Risk ◽  
Case Presentation ◽  
Nonfluent Aphasia ◽  
Protein Tau ◽  
Review Reports ◽  
Progressive Nonfluent Aphasia

<b><i>Background:</i></b> Compared to Western populations, familial frontotemporal lobar degeneration (FTLD) is rare among Asians. Progranulin (GRN) gene mutation, which is a major cause of FTLD, is likewise rare. We present a family with FTLD from the Philippines with an autosomal dominant pattern of inheritance and GRN mutation and briefly review reports of GRN mutations in Asia. <b><i>Case Presentation:</i></b> The proband is 66 years old with progressive nonfluent aphasia (PNFA)-corticobasal syndrome . We assessed 3 generations of her pedigree and found 11 affected relatives with heterogenous phenotypes, usually behavioral variant frontotemporal dementia (FTD) and PNFA. Neuroimaging showed atrophy and hypometabolism consistent with FTD syndromes. White matter hyperintensities were seen in affected members even in the absence of vascular risk factors. A GRN mutation R110X was found in 6 members, 3 with symptoms and 3 were asymptomatic. Plasma GRN was low (&#x3c;112 ng/mL) in all mutation carriers. No mutations were found in microtubule-associated protein tau, APP, PSEN1, and PSEN2 genes, and all were APOE3. <b><i>Conclusion:</i></b> This is the first Filipino family with autosomal dominant FTD documented with GRN mutation. Identifying families and cohorts would contribute to therapeutic developments in an area with FTD-GRN.

Congenital hyperinsulinism due to compound heterozygous mutations in ABCC8 responsive to diazoxide therapy

2020 ◽  
Vol 33 (5) ◽  
pp. 671-674
Author(s):  
Tashunka Taylor-Miller ◽  
Jayne Houghton ◽  
Paul Munyard ◽  
Yadlapalli Kumar ◽  
Clinda Puvirajasinghe ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Compound Heterozygous ◽  
Congenital Hyperinsulinism ◽  
Β Cells ◽  
Pancreatic Β Cells ◽  
Newborn Period ◽  
Case Presentation ◽  
Male Baby ◽  
Common Causes ◽  
Compound Heterozygous Mutations

AbstractBackgroundCongenital hyperinsulinism (CHI), a condition characterized by dysregulation of insulin secretion from the pancreatic β cells, remains one of the most common causes of hyperinsulinemic, hypoketotic hypoglycemia in the newborn period. Mutations in ABCC8 and KCNJ11 constitute the majority of genetic forms of CHI.Case presentationA term macrosomic male baby, birth weight 4.81 kg, born to non-consanguineous parents, presented on day 1 of life with severe and persistent hypoglycemia. The biochemical investigations confirmed a diagnosis of CHI. Diazoxide was started and progressively increased to 15 mg/kg/day to maintain normoglycemia. Sequence analysis identified compound heterozygous mutations in ABCC8 c.4076C>T and c.4119+1G>A inherited from the unaffected father and mother, respectively. The mutations are reported pathogenic. The patient is currently 7 months old with a sustained response to diazoxide.ConclusionsBiallelic ABCC8 mutations are known to result in severe, diffuse, diazoxide-unresponsive hypoglycemia. We report a rare patient with CHI due to compound heterozygous mutations in ABCC8 responsive to diazoxide.

The use of glimepiride for the treatment of neonatal diabetes mellitus caused by a novel mutation of the ABCC8 gene

2020 ◽  
Vol 33 (12) ◽  
pp. 1605-1608
Author(s):  
Xiao Qin ◽  
Jingzi Zhong ◽  
Dan Lan
Keyword(s):  
Diabetes Mellitus ◽  
Novel Mutation ◽  
Male Infant ◽  
Neonatal Diabetes ◽  
Monogenic Diabetes ◽  
Neonatal Diabetes Mellitus ◽  
Rare Form ◽  
Case Presentation ◽  
Abcc8 Gene

AbstractObjectivesNeonatal diabetes mellitus (NDM) is a rare form of monogenic diabetes that is usually diagnosed in the first six months of life.Case presentationWe report on a male infant with neonatal diabetes who presented with diabetic ketoacidosis at two months and 16 days. A novel homozygous missense mutation (c.259T>G) was identified in the ABCC8 gene. In this case, insulin was replaced with glimepiride at a dosage of 0.49 mg/kg/day at five months, and this achieved metabolic control and satisfactory growth as observed at follow-up.ConclusionsThis report improves our understanding of the mutational spectrum of ABCC8, which is normally associated with NDM, and shows that the treatment regimen for this condition can be successfully switched from insulin therapy to the use of sulfonylurea.

scholarly journals Copy number variation in MODY diabetes - Familial case presentation

2018 ◽  
Vol 2 (2) ◽  
pp. 73
Author(s):  
Naida Lojo-Kadric ◽  
Zelija Velija Asimi ◽  
Jasmin Ramic ◽  
Ksenija Radic ◽  
Lejla Pojskic
Keyword(s):  
Insulin Secretion ◽  
Copy Number ◽  
Autosomal Dominant ◽  
Single Gene ◽  
Maturity Onset Diabetes ◽  
Dominant Form ◽  
Case Presentation ◽  
Monogenic Diseases ◽  
Number Variation ◽  
Autosomal Dominant Form

MODY (maturity-onset diabetes of the young) is an autosomal dominant form of diabetes that is usually manifested before the 25-year of life. This type of diabetes is caused by defects in the primary insulin secretion. There are several types of MODY, which are monogenic diseases, where mutations in a single gene are responsible for a particular type of MODY. Currently, there are eleven types of MODY, from which the most common types are MODY 2 and MODY 3 (with mutations on GCK and HNF1A genes, respectively). We identified very rare MODY 7 type of diabetes in three family members by MLPA analysis.

scholarly journals Prenatal Diagnosis of Holt–Oram Syndrome With a Novel Mutation of TBX5 Gene: A Case Report

2021 ◽  
Vol 9 ◽  
Author(s):  
Guan-nan He ◽  
Xue-yan Wang ◽  
Min Kang ◽  
Xi-min Chen ◽  
Na Xi ◽  
...  
Keyword(s):  
Septal Defect ◽  
Autosomal Dominant ◽  
Novel Mutation ◽  
Splice Donor ◽  
Autosomal Dominant Disorder ◽  
Cubitus Valgus ◽  
Case Presentation ◽  
Whole Exome ◽  
The Right ◽  
Tbx5 Gene

Background: Holt–Oram syndrome (HOS) is an autosomal dominant disorder caused by mutations of TBX5 gene.Case presentation: We report a fetus with HOS diagnosed sonographically at 23 weeks of gestation. The fetal parents are non-consanguineous. The fetus exhibited short radius and ulna, inability to supinate the hands, absence of the right thumb, and heart ventricular septal defect (VSD), while the fetal father exhibited VSD and short radius and ulna only. Fetal brother had cubitus valgus and thumb adduction, except for VSD, short radius and ulna. The pregnancy was terminated. Whole-exome sequencing (WES) revealed a novel mutation in the TBX5 (c.510+1G&gt;A) in the fetus inherited from the father. The variant (c.510+1G&gt;A) occurs at splice donor and may alter TBX5 gene function by impact on splicing. It was not previously reported in China.Conclusion: Our case reported a novel mutation in TBX5, which expanded the known genetic variants associated with HOS.

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