Two unrelated Chinese patients with hyperinsulinism /hyperammonemia (HI/HA) syndrome due to mutations in glutamate dehydrogenase gene.
BACKGROUND
Hyperinsulinism/ hyperammonemia (HI/HA) syndrome is caused by excessive activity of glutamate dehydrogenase (GDH) encoded by GLUD1 gene, which oxidizes glutamate to alpha-ketoglutarate and which is a potential regulator of insulin secretion in pancreatic beta cells and of ureagenesis in the liver. So GDH is important in normal glucose homeostasis. Mutations of GDH result in HI/ HA syndrome.


METHODS
We have performed protein (leucine) and fat loading test on one patient. We detected the level of serum glucose, insulin and blood ammonia. Genomic DNA of the two patients and their parents is isolated from blood and the exons of GLUD1 gene are amplified by polymerase chain reaction (PCR) for direct sequencing.


RESULTS
The leucine diet can evocate hypoglycemia obviously. Two heterozygous mutations c.978G>A (R269H) and c.1506C>T (S445L) are identified, respectively. These are both de novo. For one patient, a better blood glucose level can be gained from leucine-restriction diet, and without diazoxide while, for the other patient, diazoxide is necessary.


CONCLUSIONS
The heterozygous mutations in GLUD1 gene can cause HI/HA syndrome, it is sensitive to the leucine. The diazoxide and leucine-restriction diet do well in controlling the blood glucose level.
Diao
Chengming
C
Key Laboratory of Endocrinology, Ministry of Health, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Chen
Shi
S
Xiao
Xinhua
X
Wang
Tong
T
Sun
Xiaofang
X
Wang
Ou
O
Song
Hongmei
H
Zhang
Yun
Y
Yu
Miao
M
Zhang
Qian
Q
Wang
Heng
H
D001786:Blood Glucose / Q000032:analysis; D002648:Child; D005969:Glutamate Dehydrogenase / Q000235:genetics*; D006801:Humans; D022124:Hyperammonemia / Q000097:blood / Q000235:genetics*; D006946:Hyperinsulinism / Q000097:blood / Q000235:genetics*; D007223:Infant; D008297:Male; D009154:Mutation
D001786:Blood Glucose; D005969:Glutamate Dehydrogenase