Información de la revista
Vol. 61. Núm. 5.
Páginas 433-437 (Noviembre 2004)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 61. Núm. 5.
Páginas 433-437 (Noviembre 2004)
Acceso a texto completo
Síndrome de hiperinsulinismohiperamoniemia por mutación de novo en el exón 7 (G979A) del gen GLUD-1,con excelente respuesta a diazóxido
Hyperinsulinism-hyperammonemia syndrome due to a de novo mutation in exon 7 (g979a) of the glutamate dehydrogenase gene with excellent response to diazoxide
Visitas
12699
C. Montero Luis, J. Pozo Román
Autor para correspondencia
jpozor@wanadoo.es

Correspondencia: Servicio de Endocrinología Pediátrica. Hospital Infantil Universitario Niño Jesús. Avda. Menéndez Pelayo, 65. 28009 Madrid. España
, M.aT. Muñoz Calvo, G. Martos Moreno, M.aA. Donoso, O. Rubio Cabezas, J. Argente Oliver
Servicio de Endocrinología Pediátrica. Departamento de Pediatría. Hospital Infantil Universitario Niño Jesús. Madrid. España
Este artículo ha recibido
Información del artículo

El síndrome de hiperinsulinismo-hiperamoniemia se caracteriza por hipoglucemias sintomáticas recurrentes en la infancia, secundarias a hiperinsulinismo, asociadas a un moderado y asintomático incremento de la amoniemia. Es debido a mutaciones en el gen de la glutamato deshidrogenasa (10q23.3), transmitidas de forma dominante, que alteran el control de la actividad enzimática y representa la segunda causa de hiperinsulinismo congénito de base conocida, siendo la primera enfermedad genética identificada debida a un aumento de la actividad de una enzima del metabolismo intermediario. Presentamos el caso de un niño de 16 meses con hipoglucemias sintomáticas recurrentes desde el final del primer año de vida, debidas a una mutación activadora de novo en el exón 7 (G979A) del gen de la GDH, con excelente respuesta terapéutica a diazóxido

Palabras clave:
Hipoglucemia
Hiperinsulinismo
Hiperamoniemia
Glutamato deshidrogenasa

Hyperinsulinism-hyperammonemia syndrome is characterized by recurrent and symptomatic hypoglycemias in childhood, secondary to hyperinsulinism associated with mild and asymptomatic hyperammonemia. This syndrome is caused by dominantly expressed mutations of the glutamate dehydrogenase gene (10q23.3). These mutations modify control of enzyme activity and represent the second cause of congenital hyperinsulinism of known genetic etiology. Moreover, this syndrome is the first genetic disorder due to an increase of function in an enzyme of intermediary metabolism to have been identified. We present the case of a 16-month-old boy with symptomatic recurrent hypoglycemias from the end of the first year of life, caused by a de novo mutation in exon 7 (G979A) of the GDH gene, with excellent outcome after diazoxide treatment

Key words:
Hypoglycemia
Hyperinsulinism
Hyperammonemia
Glutamate dehydrogenase
El Texto completo está disponible en PDF
Bibliografía
[1.]
C.A. Stanley.
Hyperinsulinism in infants and children.
Pediatr Clin North Am, 44 (1997), pp. 363-373
[2.]
B. Glaser, P. Thornton, T. Otonkoski, C. Junien.
Genetics of neonatal hyperinsulinism.
Arch Dis Child Fetal Neonatal Ed, 82 (2000), pp. F79-F86
[3.]
J.C. Fournet, C. Junien.
The genetics of neonatal hyperinsulinism.
Horm Res, 59 (2003), pp. 30-34
[4.]
C.A. Stanley, Y.K. Lieu, B.Y.L. Hsu, A.B. Burlina, C.R. Greenberg, N.J. Hopwood, et al.
Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene.
N Engl J Med, 338 (1998), pp. 1352-1357
[5.]
R.M. Sheperd, K.E. Cosgrove, R.E. O'Brien, P.D. Barnes, C. Ämmälä, M.J. Dunne.
Hyperinsulinism of infancy: Towards an understanding of unregulated insulin release.
Arch Dis Child Fetal Neonatal Ed, 82 (2000), pp. F87-F97
[6.]
M.J. Dunne.
Ions, genes and insulin release: From basic science to clinical disease.
Diabet Med, 17 (2000), pp. 91-104
[7.]
H. Huopio, F. Reimann, R. Ashfield, J. Komulainen, H.L. Lenko, J. Rahier, et al.
Dominantly inherited hyperinsulinism caused by a mutation in the sulfonylurea receptor type 1.
Clin Invest, 106 (2000), pp. 897-906
[8.]
B. Glasser, P. Kesavan, M. Heyman, E. Davis, A. Cuesta, A. Buchs, et al.
Familial hyperinsulinism caused by an activating glucokinase mutation.
N Engl J Med, 338 (1998), pp. 226-230
[9.]
E. Zammarchi, L. Filippi, E. Novembre, M.A. Donati.
Biochemical evaluation of a patient with a familial form of leucine-sensitive hypoglycemia and concomitant hyperammonemia.
Metabolism, 45 (1996), pp. 957-960
[10.]
S.A. Weinzimer, C.A. Stanley, G.T. Berry, M. Yudkoff, M. Tuchman, P.S. Thornton.
A syndrome of congenital hyperinsulinism and hyperammonemia.
J Pediatr, 130 (1997), pp. 661-664
[11.]
W.A. Cochrane, W.W. Payne, M.J. Simpkiss, L.I. Woolf.
Familial hypoglycemia precipited by amino acids.
J Clin Invest, 35 (1955), pp. 411-422
[12.]
M.M. Grumbach, S.L. Kaplan.
Amino acid and alpha-keto acid induced hyperinsulinism in the leucine sensitive type of infantile and childhood hypoglycemia.
J Pediatr, 57 (1960), pp. 346-362
[13.]
T.J. Smith, T. Schmidt, J. Fang, J. Wu, G. Siuzdak, C.A. Stanley.
The structure of apo human glutamate dehydrogenase details subunit communication and allostery.
Mol Biol, 318 (2002), pp. 765-777
[14.]
C.A. Stanley, J. Fang, K. Kutyna, B.Y. Hsu, J.E. Ming, B. Glaser, et al.
Molecular basis and characterization of the hyperinsulinism/ hyperammonemia syndrome: Predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene.
Diabetes, 49 (2000), pp. 667-673
[15.]
T. Yorifuji, J. Muroi, A. Uematsu, H. Hiramatsu, T. Momoi.
Hyperinsulinism- hyperammonemia syndrome caused by mutant glutamate dehydrogenase accompanied by novel enzyme kinetics.
Hum Genet, 104 (1999), pp. 476-479
[16.]
C. MacMullen, J. Fang, B.Y.L. Hsu, A. Kelly, P. De Lonlay-Debeney, J.M. Saudubray, et al.
Hyperinsulinism/hyperammonemia syndrome in children with regulatory mutations in the inhibitory guanosine triphosphate binding domain of glutamate dehydrogenase.
J Clin Endocrinol Metab, 86 (2001), pp. 1782-1787
[17.]
P.E. Peterson, T.J. Smith.
The structure of bovine glutamate dehydrogenase provides insights into the mechanism of allostery.
Structure Fold Des, 7 (1999), pp. 769-782
[18.]
A. Aynsley-Green, K. Hussain, J. Hall, J.M. Saudubray, C. Nihoul-Fékété, P. de Lonlay-Debeney, et al.
Practical management of hyperinsulinism in infancy.
Arch Dis Child Fetal Neonatal Ed, 82 (2000), pp. F98-F107
Copyright © 2004. Asociación Española de Pediatría
Idiomas
Anales de Pediatría
Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?