TY - JOUR
T1 - Hyperinsulinism-hyperammonemia syndrome in two Peruvian children with refractory epilepsy
AU - De Los Santos-La Torre, Miguel Angel
AU - Del Águila-Villar, Carlos Manuel
AU - Lu-De Lama, Luis Rómulo
AU - Nuñez-Almache, Oswaldo
AU - Chávez-Tejada, Eliana Manuela
AU - Espinoza-Robles, Oscar Antonio
AU - Pinto-Ibárcena, Paola Marianella
AU - Calagua-Quispe, Martha Rosario
AU - Azabache-Tafur, Pamela Miluska
AU - Tucto-Manchego, Rosa María
N1 - Publisher Copyright:
© 2022 Walter de Gruyter GmbH, Berlin/Boston.
PY - 2023/2/1
Y1 - 2023/2/1
N2 - Objectives: Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized. Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the GLUD1 gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management. Case presentation: We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru. Conclusions: HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.
AB - Objectives: Congenital hyperinsulinism (HI) is a heterogeneous clinical disorder with great variability in its clinical phenotype, and to date, pathogenic variants in 23 genes have been recognized. Hyperinsulinism-hyperammonemia syndrome (HI/HA) is the second most frequent cause of this disease that shows an autosomal dominant pattern and is caused by an activating mutation of the GLUD1 gene, which responds favorably to the use of diazoxide. HI/HA syndrome presents with fasting hypoglycemia; postprandial hypoglycemia, especially in those with a high protein content (leucine); and persistent mild hyperammonemia. Neurological abnormalities, in the form of epilepsy or neurodevelopmental delay, are observed in a high percentage of patients; therefore, timely diagnosis is crucial for proper management. Case presentation: We report the clinical presentation of two Peruvian children that presented with epilepsy whose genetic analysis revealed a missense mutation in the GLUD1 gene, one within exon 11, at 22% mosaicism; and another within exon 7, as well as their response to diazoxide therapy. To the best of our knowledge, these are the first two cases of HI/HA syndrome reported in Peru. Conclusions: HI/HA syndrome went unnoticed, because hypoglycemia was missed and were considered partially controlled epilepsies. A failure to recognize hypoglycemic seizures will delay diagnosis and adequate treatment, so a proper investigation could avoid irreversible neurological damage.
KW - congenital hyperinsulinism
KW - epilepsy
KW - hyperammonemia
KW - hypoglycemia
UR - http://www.scopus.com/inward/record.url?scp=85143758526&partnerID=8YFLogxK
U2 - 10.1515/jpem-2022-0490
DO - 10.1515/jpem-2022-0490
M3 - Article
C2 - 36476334
AN - SCOPUS:85143758526
SN - 0334-018X
VL - 36
SP - 207
EP - 211
JO - Journal of Pediatric Endocrinology and Metabolism
JF - Journal of Pediatric Endocrinology and Metabolism
IS - 2
ER -