Functional hyperactivity of hepatic glutamate dehydrogenase as a cause of the hyperinsulinism/hyperammonemia syndrome: Effect of treatment

被引:21
作者
Huijmans, JGM
Duran, M
de Klerk, JBC
Rovers, MJ
Scholte, HR
机构
[1] Erasmus Univ, Dept Clin Genet, NL-3000 DR Rotterdam, Netherlands
[2] Univ Med Ctr Het Wilhelmina Kinderziekenhuis, Utrecht, Netherlands
[3] Hosp Zeeuws Vlaanderen, Dept Pediat, Terneuzen, Netherlands
[4] Erasmus Univ, Dept Biochem, NL-3000 DR Rotterdam, Netherlands
关键词
hyperammonemia; hyperinsulinism; plasma glutamine; glutamate dehydrogenase;
D O I
10.1542/peds.106.3.596
中图分类号
R72 [儿科学];
学科分类号
100202 ;
摘要
Objective. The combination of persistent hyperammonemia and hypoketotic hypoglycemia in infancy presents a diagnostic challenge. Investigation of the possible causes and regulators of the ammonia and glucose disposal may result in a true diagnosis and predict an optimum treatment. Patient. Since the neonatal period, a white girl had been treated for hyperammonemia and postprandial hypoglycemia with intermittent hyperinsulinism. Her blood level of ammonia varied from 100 to 300 mu mol/L and was independent of the protein intake. Methods. Enzymes of the urea cycle as well as glutamine synthetase and glutamate dehydrogenase (GDH) were assayed in liver tissue and/or lymphocytes. Results. The activity of hepatic GDH was 874 nmol/ (min.mg protein) (controls: 472-938). Half-maximum inhibition by guanosine triphosphate was reached at a concentration of 3.9 mu mol/L (mean control values: .32). The ratio of plasma glutamine/blood ammonia was unusually low. Oral supplements with N-carbamylglutamate resulted in a moderate decrease of the blood level of ammonia. The hyperinsulinism was successfully treated with diazoxide. Conclusion. A continuous conversion of glutamate to 2-oxoglutarate causes a depletion of glutamate needed for the synthesis of N-acetylglutamate, the catalyst of the urea synthesis starting with ammonia. In addition, the shortage of glutamate may lead to an insufficient formation of glutamine by glutamine synthetase. As GDH stimulates the release of insulin, the concomitant hyperinsulinism can be explained. This disorder should be considered in every patient with postprandial hypoglycemia and diet-independent hyperammonemia.
引用
收藏
页码:596 / 600
页数:5
相关论文
共 20 条
[1]   Hyperinsulinism and hyperammonaemia [J].
Al-Shamsan, L ;
Al-Essa, M ;
Al-Mutair, A ;
Al-Ashwal, A ;
Sakati, N ;
Ozand, PT .
JOURNAL OF INHERITED METABOLIC DISEASE, 1998, 21 (06) :671-673
[2]   GLUTAMATE STIMULATES INSULIN-SECRETION AND IMPROVES GLUCOSE-TOLERANCE IN RATS [J].
BERTRAND, G ;
PUECH, R ;
LOUBATIERESMARIANI, MM ;
BOCKAERT, J .
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 1995, 269 (03) :E551-E556
[3]   NEONATAL HYPERAMMONEMIA CAUSED BY A DEFECT OF CARNITINE-ACYLCARNITINE TRANSLOCASE [J].
DEBAULNY, HO ;
SLAMA, A ;
TOUATI, G ;
TURNBULL, DM ;
POURFARZAM, M ;
BRIVET, M .
JOURNAL OF PEDIATRICS, 1995, 127 (05) :723-728
[4]   Glucose regulation of glutaminolysis and its role in insulin secretion [J].
Gao, Z ;
Li, GZ ;
Najafi, H ;
Wolf, BA ;
Matschinsky, FM .
DIABETES, 1999, 48 (08) :1535-1542
[5]   Muscular origin of hyperammonaemia [J].
Kamoun, P ;
Rabier, D ;
Saudubray, JM .
EUROPEAN JOURNAL OF PEDIATRICS, 1998, 157 (10) :868-868
[6]  
Kanamori K, 1996, J NEUROCHEM, V67, P1584
[7]   Hyperinsulinaemic hypoglycaemia associated with persistent hyperammonaemia [J].
Kitaura, J ;
Miki, Y ;
Kato, H ;
Sakakihara, Y ;
Yanagisawa, M .
EUROPEAN JOURNAL OF PEDIATRICS, 1999, 158 (05) :410-413
[8]   Hyperinsulinism plus hyperammonemia [J].
Parini, R ;
Colombo, F ;
Lombardi, AM ;
Omati, S ;
Menni, F ;
Beccaria, L .
JOURNAL OF PEDIATRICS, 1998, 133 (06) :800-801
[9]  
PERMUTT MA, 1996, DIABETES REV, V4, P347
[10]  
ROE TF, 1982, PEDIATR RES, V16, P1