A case of hyperinsulinism/hyperammonaemia syndrome: usefulness of the oral protein tolerance for the evaluation of treatment

Toriumi, Yoshitaka; Murata, Kohji; Taketani, Takeshi; Uchiyama, Atsushi; Ohie, Takaharu; Yamaguchi, Seiji

doi:10.1007/s00431-004-1592-9

Cited by 4 publications

(7 citation statements)

References 8 publications

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“…Interestingly, five of the six HI/HA subjects who developed hypoglycemia (<50 mg/dL) during a controlled fast had appropriate (<2 μIU/mL) plasma insulin levels ( 21 ). Similarly, a patient who experienced hypoglycemia during a monitored fast also had suppressed plasma insulin concentrations ( 24 ). The fasted humanized hGDH H454Y mice had lower plasma glucose concentrations ( Figs.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, during the hypoglycemia following a controlled fast, plasma insulin concentrations were often appropriately suppressed. These indicate that insulin per se is not the sole driver of hypoglycemia, and another uncharacterized insulin-independent hypoglycemic factor must be involved ( 3 , 21 , 22 , 24 ).…”

Section: Introductionmentioning

confidence: 98%

“…The biochemical diagnosis of HI/HA is aided by dramatic hyperinsulinemia following intravenous leucine infusion ( 2 , 20 ). Nevertheless, in the more physiologically relevant scenario of a protein-rich meal, an unexplained observation in HI/HA is that hypoglycemia can develop despite the same plasma insulin response as control subjects ( 23 , 24 ).…”

Section: Introductionmentioning

confidence: 99%

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Mitochondrial GTP Insensitivity Contributes to Hypoglycemia in Hyperinsulinemia Hyperammonemia by Inhibiting Glucagon Release

et al. 2014

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Mitochondrial GTP (mtGTP)-insensitive mutations in glutamate dehydrogenase (GDHH454Y) result in fasting and amino acid–induced hypoglycemia in hyperinsulinemia hyperammonemia (HI/HA). Surprisingly, hypoglycemia may occur in this disorder despite appropriately suppressed insulin. To better understand the islet-specific contribution, transgenic mice expressing the human activating mutation in β-cells (H454Y mice) were characterized in vivo. As in the humans with HI/HA, H454Y mice had fasting hypoglycemia, but plasma insulin concentrations were similar to the controls. Paradoxically, both glucose- and glutamine-stimulated insulin secretion were severely impaired in H454Y mice. Instead, lack of a glucagon response during hypoglycemic clamps identified impaired counterregulation. Moreover, both insulin and glucagon secretion were impaired in perifused islets. Acute pharmacologic inhibition of GDH restored both insulin and glucagon secretion and normalized glucose tolerance in vivo. These studies support the presence of an mtGTP-dependent signal generated via β-cell GDH that inhibits α-cells. As such, in children with activating GDH mutations of HI/HA, this insulin-independent glucagon suppression may contribute importantly to symptomatic hypoglycemia. The identification of a human mutation causing congenital hypoglucagonemic hypoglycemia highlights a central role of the mtGTP–GDH–glucagon axis in glucose homeostasis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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Mitochondrial GTP Insensitivity Contributes to Hypoglycemia in Hyperinsulinemia Hyperammonemia by Inhibiting Glucagon Release

et al. 2014

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“…Toriumi et al. demonstrated that excessive insulin secretion was suppressed and hypoglycaemia improved after giving several days of oral diazoxide (3.3 mg/kg/day) to patients with HI/HA syndrome before conducting a protein tolerance test (egg and cheese containing 100 mg/kg of leucine) 9 …”

Section: Discussionmentioning

confidence: 99%

Hyperinsulinism and hyperammonaemia syndrome due to a novel missense mutation in the allosteric domain of the Glutamate dehydrogenase 1 gene

Chik

Chan

Lam

et al. 2008

J Paediatrics Child Health

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“…In 2002, in a multicenter series of 175 patients, hyperammonaemia was found in 12 out of 69 tested patients with hyperinsulinemic hypoglycemia (12). Although the disease is rare, several case reports and some reviews have been published (2,9,(13)(14)(15)(16)(17)(18)). An interesting clinical aspect of HI-HA syndrome is that epilepsy is a frequent finding; in a cohort of 16 patients, 15 presented seizures and 43% of them developed epilepsy.…”

Section: G6pmentioning

confidence: 99%

Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene

Corrêa-Giannella

Freire

Cavaleiro

et al. 2012

Arq Bras Endocrinol Metab

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SUMMARYThe hyperinsulinism/hyperammonemia (HI/HA) syndrome is a rare autosomal dominant disea se manifested by hypoglycemic symptoms triggered by fasting or highprotein meals, and by elevated serum ammonia. HI/HA is the second most common cause of hyperinsulinemic hypo glycemia of infancy, and it is caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Biochemical evaluation, as well as direct sequencing of exons and exonintron boundary regions of the GLUD1 gene, were per formed in a 6year old female patient presenting fasting hypoglycemia and hyperammonemia. The patient was found to be heterozygous for one de novo missense mutation (c.1491A>G; p.Il497Met) previously reported in a Japanese patient. Treatment with diazoxide 100 mg/day promoted complete resolution of the hypoglycemic episodes. Arq Bras Endocrinol Metab. 2012;56(8):485-9 SUMÁRIO A síndrome de hiperinsulinemia/hiperamonemia (HI/HA) é uma condição rara, de herança autos sômica dominante, que se manifesta por sintomas de hipoglicemia desencadeada por je jum ou refeições de alto conteúdo proteico, juntamente com elevação da concentração de amô nia sérica. HI/HA é a segunda causa de hipoglicemia hiperinsulinêmica da infância e é causa da por mutações ativadoras no GLUD1, o gene que codifica a enzima mitocondrial glutamato desidrogenase (GDH). A avaliação bioquímica, bem como o sequenciamento direto dos éxons e junções éxoníntron do gene GLUD1, foi realizada em uma paciente de 6 anos de idade com hi poglicemia de jejum e hiperamonemia. A paciente apresentava uma mutação de novo missense (c.1491A>G; p.Il497Met) em heterozigose, que havia sido previamente relatada em um paciente japonês. O tratamento com diazóxido 100 mg/dia promoveu resolução completa dos episódios hipoglicêmicos. Arq Bras Endocrinol Metab. 2012;56(8):485-9

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A case of hyperinsulinism/hyperammonaemia syndrome: usefulness of the oral protein tolerance for the evaluation of treatment

Cited by 4 publications

References 8 publications

Mitochondrial GTP Insensitivity Contributes to Hypoglycemia in Hyperinsulinemia Hyperammonemia by Inhibiting Glucagon Release

Mitochondrial GTP Insensitivity Contributes to Hypoglycemia in Hyperinsulinemia Hyperammonemia by Inhibiting Glucagon Release

Hyperinsulinism and hyperammonaemia syndrome due to a novel missense mutation in the allosteric domain of the Glutamate dehydrogenase 1 gene

Hyperinsulinism/hyperammonemia (HI/HA) syndrome due to a mutation in the glutamate dehydrogenase gene

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