Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2

Cabezas, Oscar Rubio; Flanagan, Sarah E.; Stanescu, Horia; García‐Martínez, Elena; Caswell, Richard; Allen, Hana Lango; Antón‐Gamero, Montserrat; Argente, Jesús; Bussell, Anna Marie; Brändli, André W.; Cheshire, Chris; Crowne, Elizabeth; Dumitriu, Simona; Drynda, Robert; Shield, Julian P H; Hayes, Wesley; Hofherr, Alexis; Iancu, Daniela; Issler, Naomi; Jefferies, Craig; Jones, Peter M.; Johnson, Matthew; Kesselheim, Anne; Klootwijk, Enriko; Koettgen, Michael; Lewis, W; Martos, José María; Mozere, Monika; Norman, Jill T.; Patel, Vaksha; Parrish, Andrew; Pérez‐Cerdá, Celia; Pozo, Juan Ignacio; Rahman, Sofia; Sebire, Neil J.; Tekman, Mehmet; Turnpenny, Peter D.; Hoff, William van’t; Viering, Daan; Weedon, Michael N.; Wilson, Patricia D.; Guay‐Woodford, Lisa M.; Kleta, Robert; Hussain, Khalid; Ellard, Sian; Böckenhauer, Detlef

doi:10.1681/asn.2016121312

Cited by 102 publications

(90 citation statements)

References 43 publications

(45 reference statements)

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“…Activating gene mutations in CACNA1D encoding the voltage-gated Ca 2+ channels have been reported; inappropriate channel activation has been postulated to cause unregulated Ca 2+ entry into the b cell to trigger insulin secretion [18]. Another mutation in the promoter region of PMM2 encoding phosphomannomutase 2, a key enzyme in protein glycosylation, also affects b-cell function by unknown mechanisms [19].…”

Section: Genetic Forms Of Congenital Hyperinsulinismmentioning

confidence: 99%

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

et al. 2018

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Congenital hyperinsulinism is a rare disease, but is the most frequent cause of persistent and severe hypoglycaemia in early childhood. Hypoglycaemia caused by excessive and dysregulated insulin secretion (hyperinsulinism) from disordered pancreatic β cells can often lead to irreversible brain damage with lifelong neurodisability. Although congenital hyperinsulinism has a genetic cause in a significant proportion (40%) of children, often being the result of mutations in the genes encoding the KATP channel (ABCC8 and KCNJ11), not all children have severe and persistent forms of the disease. In approximately half of those without a genetic mutation, hyperinsulinism may resolve, although timescales are unpredictable. From a histopathology perspective, congenital hyperinsulinism is broadly grouped into diffuse and focal forms, with surgical lesionectomy being the preferred choice of treatment in the latter. In contrast, in diffuse congenital hyperinsulinism, medical treatment is the best option if conservative management is safe and effective. In such cases, children receiving treatment with drugs, such as diazoxide and octreotide, should be monitored for side effects and for signs of reduction in disease severity. If hypoglycaemia is not safely managed by medical therapy, subtotal pancreatectomy may be required; however, persistent hypoglycaemia may continue after surgery and diabetes is an inevitable consequence in later life. It is important to recognize the negative cognitive impact of early‐life hypoglycaemia which affects half of all children with congenital hyperinsulinism. Treatment options should be individualized to the child/young person with congenital hyperinsulinism, with full discussion regarding efficacy, side effects, outcomes and later life impact.

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Section: Genetic Forms Of Congenital Hyperinsulinismmentioning

confidence: 99%

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

et al. 2018

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“…CHI is caused by variants in genes such as ABCC8 [7], KCNJ11 [8], GLUD1 [9], HADH1 [10], GCK [11], PGM1 [12], HK1 [13], HNF4A [14], HNF1A [15], SLC16A1 [16], PMM2 [17], FOXA2 [18], INSR [19], and possibly UCP2 [20,21] and CACNA1D [22]. In addition, some genetic syndromes such as Beckwith-Wiedemann, Kabuki, and Turner syndromes are associated with hyperinsulinism [23,24].…”

Section: Introductionmentioning

confidence: 99%

Congenital Hyperinsulinism Caused by Novel Homozygous K<sub>ATP</sub> Channel Gene Variants May Be Linked to Unexplained Neonatal Deaths among Kurdish Consanguineous Families

et al. 2020

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Congenital hyperinsulinism (CHI) is a potentially life-threatening cause of severe hypoglycemia in the neonatal and infant period. • The incidence of CHI has been estimated to be around 1 in 50,000 in non-consanguineous populations and as high as 1 in 2,500 in areas with a higher rate of consanguinity. • Certain countries with high rates of consanguinity have a much higher infant and neonatal mortality rate than the rest of the world. Novel Insights• Three novel homozygous variants are reported in genes ABCC8 and KCNJ11 causing CHI in three Kurdish consanguineous families. Two of these families have a notable history of unexplained neonatal deaths. • A small but significant percentage of all unexplained neonatal deaths could be due to undiagnosed CHI. Therefore, especially in regions with a high prevalence of consanguinity, undiagnosed CHI can contribute to higher infant and neonatal mortality rates. AbstractIntroduction: Neonatal hypoglycemia due to congenital hyperinsulinism (CHI) is a potentially life-threatening condition. Biallelic pathogenic variants in K ATP channel subunit genes (ABCC8, KCNJ11), causing severe forms of CHI, are more prevalent in regions with a significant rate of consanguinity and may lead to unexplained neonatal deaths. We hypothesized that K ATP channel gene variants are the cause of CHI in three unrelated children from consanguineous

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“…CHI is a heterogeneous disorder with respect to clinical presentation, imaging, histology, and genetics. Mutations in at least 11 different genes ( ABCC8 , KCNJ11 , GLUD1 , GCK , HADH , SLC16A1 , UCP2 , HNF4A , HNF1A , PMM2 , and HK ) have been reported so far as the genetic causes of CHI [1-5]. There are 2 main histological types of CHI: diffuse and focal; these are clinically identical but differ in the underlying genetic mechanism, histopathology, and management.…”

Section: Introductionmentioning

confidence: 99%

The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia

et al. 2018

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Background: A long-acting somatostatin analogue (lanreotide) is used in the management of a diazoxide-unresponsive diffuse form of congenital hyperinsulinism (CHI). However, no reports of its use in patients with the focal form of CHI exist. Case 1: A 1-month-old boy diagnosed with diazoxide-unresponsive CHI due to a paternal heterozygous ABCC8 gene mutation showed partial response to octreotide. ¹⁸F-DOPA-PET/CT scan revealed a focal lesion in the pancreatic head. Surgical removal of the lesion was unsuccessful. He was switched to monthly lanreotide treatment at the age of 11 months, which stabilised his blood glucose over a 12-month period. Case 2: A 1-month-old boy with diazoxide-unresponsive CHI due to a paternal heterozygous KCNJ11 gene mutation was partially responsive to octreotide. ¹⁸F-DOPA-PET/CT scan confirmed a focal pancreatic head lesion. Over 6 months, he underwent 3 lesionectomies and afterwards responded to octreotide. At the age of 9 months, treatment was switched to monthly lanreotide. Currently, he is aged 3, with stable glycaemia, and improved fasting tolerance. Case 3: A 3-week-old girl with a paternal heterozygous ABCC8 gene mutation was unresponsive to diazoxide. ¹⁸F-DOPA-PET/CT scan confirmed a focal pancreatic head lesion. She responded to octreotide, and her parents preferred to avoid pancreatic surgery. At the age of 20 months, treatment was switched to monthly lanreotide, resulting in euglycaemia over the last 7 months. Conclusion: CHI patients with focal pancreatic head lesions are challenging, especially if not surgically amenable. Conservative treatment is preferable, and lanreotide might be an option. The therapeutic impact of lanreotide treatment in patients with the focal forms of CHI should be confirmed in prospective studies with close monitoring of the side effects.

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Polycystic Kidney Disease with Hyperinsulinemic Hypoglycemia Caused by a Promoter Mutation in Phosphomannomutase 2

Cited by 102 publications

References 43 publications

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

Therapies and outcomes of congenital hyperinsulinism‐induced hypoglycaemia

Congenital Hyperinsulinism Caused by Novel Homozygous K<sub>ATP</sub> Channel Gene Variants May Be Linked to Unexplained Neonatal Deaths among Kurdish Consanguineous Families

The Use of a Long-Acting Somatostatin Analogue (Lanreotide) in Three Children with Focal Forms of Congenital Hyperinsulinaemic Hypoglycaemia

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