Fatal cerebral edema associated with serine deficiency in CSF
A 4-year-old girl with normal mental development suffered from asthma for which she used Flixotide (a steroid, 2 dd 250 µg) and salmeterol (2 dd 25 µg). She had normal height but severe malnutrition [weight < 2 standard deviations (SD)] due to feeding difficulties related to behavioral problems. Because of sleep disturbances, the patient had been on treatment with Alimemazine (an antihistaminic sedative agent) for 4 months. Two days before her death (in the evening, day 1), she presented with fever (39–40°C) without other particularities. The next morning (day 2), she was found in bed with tonic clonic seizures. The seizures were resistant to multiple anticonvulsive drugs. There were no signs of respiratory or circulatory failure. On admission, serum glucose was 4.0 mmol/L, with CSF glucose 1.0 mmol/L; serum electrolytes were normal, as was blood ammonia (15 µmol/l). There were no signs of a bacterial central nervous system (CNS) infection in CSF, no pleocytosis, and bacterial and viral cultures remained negative; later nasal cultures, however, showed an adenovirus V. Blood C-reactive protein (CRP) was > 300 mg/ml.\nPhysical examination showed a very ill girl with coma scores E1, M4, V1. Intubation and cardiac support were effective for some hours, but a rapid deterioration was seen with an isoelectric electroencephalogram (EEG) pattern and absent stem reflexes. After a repeated isoelectric EEG, the next day, supportive treatment was discontinued. No postmortem examination was performed. Metabolic investigations in plasma and CSF taken at day 2 showed particularly low plasma and CSF serine concentrations. Concentrations of the other amino acids were normal or decreased according to a nonspecific pattern (data not shown). Unfortunately, no fibroblasts were available for analysis of 3-PGDH activity. Plasma lactate and 3-hydroxybutyrate were clearly increased, as was CSF lactate (Table ). Urine organic acid analysis showed a moderate ketonuria as well as a marginally elevated lactate excretion.