Glutamate Dehydrogenase (GLUD1) 유전자 돌연변이에 의한 HI/HA 증후군 1례
A Case of Hyperinsulinism/Hyperammonemia (HI/HA) Syndrome due to a Mutation in the Glutamate Dehydrogenase Gene (GLUD1)
0
조회
0
다운로드
1
인용
0
참고문헌
키워드
초록
HI/HA 증후군은 선천성 고인슐린혈증의 한 형태로 GLUD1 유전자의 돌연변이에 의하여 발생한다. 고인슐린성 저혈당이 고암모니아혈증과 동반되는 것이 특징이다. 6개월 남아가 금식 시 저혈당에 의한 경련이 있었는데 경련 당시 혈당과 혈중 암모니아 수치는 각각 17 mg/dL, 203 μmol/L 이었다. 정상적으로 식이를 진행하였으나 혈당이 50 mg/dL 미만으로 저하되어 고암모니혈증과 동반된 고인슐린혈증에 의한 저혈당증을 의심하였다. GLUD1 유전자 직접 염기서열 분석에서 c.1337G˃A (p.Gly446Asp) 돌연변이를 확인하였다. Diazoxide 를 복용하기 시작하였으며 혈당이 정상범위로 유지되었다. HI/HA 증후군은 KATP 통로에 의한 CHI보다 임상 증상이 경하고 diazoxide 치료에 반응하므로 조기에 진단하여 치료를 시작하는 것이 저혈당에 의한 뇌손상을 예방하기 위해 중요하다. 발달 지연, 인지 장애 등이 HI/HA 증후군과 동반될 수가 있어 치료를 계속하면서 환자의 성장과 발달 상태에 대한 정기적인 평가를 시행하여야 하겠다.
Abstract
Hyperinsulinism/Hyperammonemia (HI/HA) syndrome is a form of congenital hyperinsulinism (CHI) caused by a mutation in the GLUD1 gene. It is characterized by hyperinsulinemic hypoglycemia accompanying hyperammonemia. A 6-month-old male infant presented with seizure caused by fasting-induced hypoglycemia. At the time of seizure, the serum glucose and ammonia levels were 17 mg/dL and 203 μmol/L, respectively. Even though he was fed as usual, his blood glucose level reduced to below 50 mg/dL with an increased plasma insulin level. He was thought to have hyperinsulinemic hypoglycemia associated with hyperammonemia. Analysis of the GLUD1 gene revealed a heterozygous c.1337G˃A (p.Gly446Asp) mutation. He was administered diazoxide, following which his blood glucose levels were maintained within the normal range. Because HI/HA syndrome is a diazoxide-responsive form of CHI, early detection and appropriate management are important to prevent brain injury. Since patients with HI/HA syndrome may have neurological complications such as developmental delay, and cognitive impairment, careful and repeated neurologic evaluation is needed.
참고문헌 (28)
- Leibowitz G, "Hyperinsulinemic hypoglycemia of infancy (nesidioblastosis) in clinical remession: high incidence of diabetes mellitus and persistent β-cell dysfunction at long-term follow- up", J Clin Endocrinol Metab, 80, pp.386~392 (1995)
- Glaser B, "Genetics of neonatal hyperinsulinism", Arch Dis Child Fetal Neonatal Ed, 82, pp.79~86 (2000)
- Kapoor RR, "Hyperinsulinaemic hypoglycaemia", Arch Dis Child, 94, pp.450~457 (2009)
- Stanley CA, "Molecular basis and characterization of the hyperinsulinism", hyperammonemia syndrome: predominance of mutations in exons 11 and 12 of the glutamate dehydrogenase gene, 2000, pp.49, 667~673
- de Lonlay P, "Hyperinsulinism and hyperammonemia syndrome: report of twelve unrelated patients", Pediatr Res, 50, pp.353~357 (2001)
- de Lonlay P, "Heterogeneity of persistent hyperinsulinaemic hypoglycaemia. A series of 175 cases", Eur J Pediatr, 161, pp.37~48 (2002)
- The Korean Pediatric Society, "Korean infant development screening test" (2002), Kwangmun Co
- Hussain K, "Diagnosis and management of hyperinsulinaemic hypoglycaemia of infancy", Horm Res, 69, pp.2~13 (2008)
- Thomas PM, "Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy", Science, 268, pp.426~429 (1995)
- Thomas P, "Mutation of the pancreatic islet inward rectifier Kir6.2 also leads to familial persistent hyperinsulinemic hypoglycemia of infancy", Hum Mol Genet, 5, pp.1813~1822 (1996)
- Taschenberger G, "Identification of a familial hyperinsulinism-causing mutation in the sulfonylurea receptor 1 that prevents normal trafficking and function of KATP channels", J Biol Chem, 277, pp.17139~17146 (2002)
- Huopio H, "K(ATP) channels and insulin secretion disorders", Am J Physiol Endocrinol Metab, 283, pp.207~216 (2002)
- Stanley CA, "Hyperinsulinism and hyperammonemia in infants with regulatory mutations of the glutamate dehydrogenase gene", N Engl J Med, 338, pp.1352~1357 (1998)
- Clayton PT, "Hyperinsulinism in short-chain L-3- hydroxyacyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion", J Clin Invest, 108, pp.457~465 (2001)
- James C, "The genetic basis of congenital hyperinsulinism", J Med Genet, 46, pp.289~299 (2009)
- Sung JY, "A case of hyperinsulinism", hyperammonemia syndrome, 2005, pp.10, 236~240
- MacMullen C, "Hyperinsulinism", hyperammonemia contributing investigators : Hyperinsulinism, J Clin Endocrinol Metab, pp.2001, 86[DOI]
- Valayannopoulos V, "What’s new in metabolic and genetic hypoglycaemias: diagnosis and management", Eur J Pediatr, 167, pp.257~265 (2008)
- Aynsley-Green A, "Practical management of hyperinsulinism in infancy", Arch Dis Child Fetal Neonatal Ed, 82, pp.98~107 (2000)
- Clayton PT, "Hyperinsulinism in short-chain L-3- hydroxy-acyl-CoA dehydrogenase deficiency reveals the importance of beta-oxidation in insulin secretion", J Clin Invest, 108, pp.457~465 (2001)
- Stanley CA, "Hyperinsulinism", hyperammonemia syndrome: insights into the regulatory role of glutamate dehydrogenase in ammonia metabolism, 2004, pp.81, 45~51
- De Leon DD, "Mechanisms of disease: advances in diagnosis and treatment of hyperinsulinism in neonates", Nat Clin Pract Endocrinol Metab, 3, pp.57~68 (2007)
- Glaser B, "Persistent hyperinsulinaemic hypoglycaemia of infancy: long-term treatment with the somatostatin analogue Sandostatin", Clin Endocrinol, 31, pp.71~80 (1989)
- Bas F, "Successful therapy with calcium channel blocker (nifedipine) in persistent neonatal hyperinsulinemic hypoglycemia of infancy", J Pediatr Endocrinol Metab, 12, pp.873~878 (1999)
- Yasuda K, "A Japanese case of congenital hyperinsulinism with hyperammonemia due to a mutation in glutamate dehydrogenase (GLUD1) gene", Intern Med, 40, pp.32~37 (2001)
- Raizen DM, "Central nervous system hyperexcitabiliy associated with glutamate dehydrogenase gain of function mutations", J Pediatr, 146, pp.388~394 (2005)
- Bahi-Buisson N, "Myoclonic absence epilepsy with photosensitivity and a gain of function mutation in glutamate dehydrogenase", Seizure, 17, pp.658~664 (2008)
- Bahi-Buisson N, "Neurological aspects of hyperinsulinism-hyperammonaemia syndrome", Dev Med Child Neurol, 50, pp.945~949 (2008)