© 2003 Diabetes UK. Diabetic Medicine, 20, 481– 482 481 Introduction In normal physiological conditions, the human brain relies entirely on glucose for its high energy requirements. Lack of glucose results in compromised brain function ranging from mild confusion to life-threatening seizures and coma. These ‘neuroglycopenic’ signs are frequently encountered when hypoglycaemia occurs in patients with insulin-treated diabetes mellitus. The other extreme of metabolic derangement in diabetes mellitus is ketoacidosis. Physicians generally consider ketoac- idosis as a potential threat to their patients. It is associated with diabetic coma and also prolonged vomiting or fasting, and alcoholism, and requires prompt treatment to restore meta- bolic balance. However, it is less widely appreciated that ketosis is an important physiological response to maintain brain energy metabolism during prolonged fasting. Here we report a patient with recurrent neuroglycopenia due to defective glucose transport into brain, and the benefit of ketosis in this condition. Case report An 18-year-old girl with non-progressive motor and mental handicaps characterized as ‘spastic-ataxic quadriplegia’ suffered from paroxysms consisting of misty eyes, absent- mindedness, slurred speech, impaired swallowing, and hypo- tonia. These seizure-like events started at the age of 2 years and occurred shortly before meals. The parents succeeded in preventing these episodes without anticonvulsant medication by offering small meals in regular time intervals. Definite epileptic seizures were never observed, and repeated electro- encephalographic studies never showed epileptiform activity. The ‘fits’ were interpreted as neuroglycopenia due to hypogly- caemia, caused by hyperinsulinism. However, extensive and repeated laboratory investigations, and a metabolic and endocrinological work-up including repeated fasting tests and glucose loading tests never led to a diagnosis. Most importantly, blood glucose levels were always found to be normal during these events. This girl came to our attention when we repeated a retro- spective study described previously [1], looking for unexplained hypoglycorrhachia, i.e. a low glucose concentration in cere- brospinal fluid (CSF) in the presence of normoglycaemia. This constellation is characteristic of GLUT1 deficiency syndrome caused by impaired glucose transport into brain via the facili- tated glucose transporter GLUT1. In the patient described, this isolated hypoglycorrhachia with otherwise normal CSF para- meters was found at the age of 2 years (CSF glucose 1.2 mmol / l and blood glucose 4.0 mmol/l, ratio 0.3), and 6 years (CSF glucose 1.4 mmol / l and blood glucose 4.2 mmol / l, ratio 0.33). The diagnosis was confirmed by demonstrating defective glucose uptake into the patient’s erythrocytes [1–3]. After establishing the diagnosis we discussed the possibil- ities of treating the patient with a ketogenic diet. Unfortunately, preparation of the meals proved to be impossible in the patient’s residence. Discussion GLUT1 deficiency syndrome results from impaired glucose transport into brain mediated by the facilitative glucose Correspondence to: M. A. A. P. Willemsen MD, PhD, University Medical Centre Nijmegen, Department of Paediatric Neurology, 945 IKNC, PO Box 9101, 6500 HB Nijmegen, the Netherlands. E-mail: m.willemsen@cukz.umcn.nl Abstract We report a patient with recurrent symptoms of neuroglycopenia due to a de- fective glucose transport into brain. The potential benefit of ketosis in neuro- glycopenia is discussed from the therapeutic concept of a ketogenic diet in GLUT1-deficiency syndrome. Diabet. Med. 20, 481– 482 (2003) Keywords GLUT1-deficiency syndrome, ketogenic diet, ketosis, neuroglycopenia Blackwell Publishing Ltd. Oxford, UK DME Diabetic Medicine 0742-3071 Blackwell Science Ltd, 2003 20 Case Report Case report Neuroglycopenia in normoglycaemic patients M. A. A. P. Willemsen et al. Neuroglycopenia in normoglycaemic patients, and the potential benefit of ketosis M. A. A. P. Willemsen, R. J. Soorani-Lunsing*, E. Pouwels* and J. Klepper† Department of Paediatric Neurology, University Medical Centre Nijmegen, Nijmegen and *Department of Paediatric Neurology, University Medical Centre Groningen, Groningen, the Netherlands, and †Department of Paediatric Neurology, University Children’s Hospital, Essen, Germany Accepted 13 February 2003