Hyperinsulinism/hyperammonaemia (HI/HA) syndrome (OMIM 606762) was first reported by Zammarchi et al. [7] and Weinzimer et al. [6] in the late 1990 s as cases of hyperinsulinism with hypoglycaemia having persistently high plasma ammonium levels. In 1998, Stanley et al. [4] reported that HI/HA syndrome is caused by mutations in the glutamate dehydrogenase (GDH) gene [4]. It is known that the occurrence of HI/HA is as follows [3]. As the result of the overactivity of GDH, a mitochondrial matrix enzyme, there is an increase in the ATP/ADP ratio and a reduction in glutamate using NAD or NADP as a coenzyme. Leucine acts as an activator of GDH resulting in hyperinsulinism. Hyperammonaemia results from the decrease in glutamate which in turn decreases the level of N-acetylglutamate, an activator of carbamoyl-phosphate synthetase, the first step in ammonia metabolism. HI/HA syndrome is considered to be an autosomal dominant inherited disorder, although a de novo mutation is often observed. Administration of diazoxide, which inhibits insulin secretion, is considered to be an effective treatment for HI/HA syndrome [2,5]. The present study reports our experience of a case of HI/ HA syndrome in which the oral protein tolerance test was useful in evaluation of treatment. The patient was a girl aged 6 years and 3 months. At the age of 4 years and 1 month, when she had an episode of diarrhoea, her family noticed that she was unsteady and could not articulate. At a local hospital, intravenous glucose infusion resulted in a rapid improvement. As blood glucose was 23 mg/dl and urinary ketones were demonstrated (4+), a diagnosis of ‘‘ketotic hypoglycaemia’’ was made. Thereafter, during occasional upper respiratory tract infections, blood glucose levels often dropped below 50 mg/dl. At the age of 6 years, symptoms such as abnormal eye movements and body sway after lunch became increasingly frequent. At this stage, the patient who was thought to be experiencing hypoglycaemic episodes, was referred to our medical centre. In terms of family history, her mother (34 years old) had hypoglycaemia when she was young. The patient’s physical development had been normal, but she had always been restless. On examination, height was 113.2 cm (-0.34 SD) and weight was 23.0 kg (obesity index 14%), and the physical examination was unremarkable, with neither hepatomegaly nor splenomegaly observed. Clinical laboratory tests on admission revealed hypoglycaemia (blood glucose 44 mg/dl) and hyperammonaemia (NH3 212 lg/dl) with no other abnormalities. Blood ketone bodies and free fatty acids were within the appropriate reference ranges. Plasma insulin level (IRI) was normal (3.1 lU/ml), and levels of pituitary hormones, cortisol, thyroid hormones, and glucagon were unremarkable. Venous blood gas analysis and urinalysis revealed no abnormality. Prior to the current admission, she had been brought straight from kindergarten to the emergency department of our hospital at the age of 5 years. At that time, blood biochemistry showed the following results: glucose 23 mg/dl; IRI 19.2 lU/ml; and NH3 184 lg/dl. On recovery, she had been followed up on an outpatient basis and fasting biochemistry revealed the following: glucose 52 mg/dl; IRI 2.1 lU/ml; NH3 183 lg/dl, and ketone bodies 99 nmol/ml. Analysis of urinary organic acids demonstrated only a mild to moderate increase in ketone bodies during hypoglycaemic attacks. Acylcartinine analysis by tandem mass spectrometry showed no particular abnormality. Moreover, analysis of blood amino acids during a hypoglycaemic attack was unremarkable. In terms of diagnostic imaging, ultrasound and CT revealed no abnormality of the liver, pancreas, or portal vein. The level of insulin was high (19.2 lU/ml) Y. Toriumi (&) AE K. Murata AE T. Taketani AE A. Uchiyama T. Ohie AE S. Yamaguchi Department of Paediatrics, Shimane University School of Medicine, Izumo, Japan E-mail: toriumi@r3.dion.ne.jp Tel.: +81-852-278111 Fax: +81-852-278119