A previously healthy 3-year-old girl was admitted to the Emergency Department (ER) because of seizures and drowsiness. Three days before the ER visit, she had respiratory symptoms and her oral intake had been poor. The day before the visit, she had a fever and had taken medicines including Cefcapene Pivoxil HCl Hydrate (FLOMOX Fine granules for children 100 g, Ildong, Seoul, Korea) 2 doses. Her mother said that she had been relatively good in daytime and went to bed supperless. About 5 o'clock in the morning, one hour before the ER visit, she woke up with cold sweating and became irritable and drowsy. Generalized tonic-clonic type seizures developed en route to the hospital. She was born by Caesarean at full-term age and a weight of 3.8 kg. She was the first-born to nonconsanguineous parents. Her growth and developmental status was appropriate for the same age. Her mother said that newborn screening test and past medical history was unremarkable. She has a younger sister with normal growth development and no other symptoms or signs.
At the ER, physical examination findings included her height 104 cm (75th–90th percentile), weight 16.5 kg (75th percentile), body mass index 15.26 kg/m
2 (50th percentile), heart rate 110/min, respiratory rate 24/min, body temperature was 37.7℃. She was in a state of tonic-clonic seizures and conscious level was deeply drowsy. Head and neck examination showed slight dried tongue, normal tympanic membrane and no palpable neck lymph nodes. On examination of the chest, breath and heart sounds were normal. Abdominal examination showed normal bowel sounds, without tenderness on palpation, and not apparent hepatosplenomegaly. There was no edema on extremity or rashes on the skin. Laboratory finding showed the following results: white blood cell 30.5 ×10
3/µL (reference range [RR], 5.5–15.5 ×10
3/µL), hemoglobin 11.8 g/dL (RR, 11.5–13.5 g/dL), platelet count 459 10
9/L (RR, 150–450 10
9/L), erythrocyte sedimentation rate 25 mm/hr (RR, 0–20 mm/hr), C-reactive protein 4.23 mg/dL (RR, 0.0–0.5 mg/dL), aspartate aminotransferase 47 U/L (RR, 13–35 U/L), alanine aminotransferase 16U/L (RR, 7–35 U/L), total cholesterol 156 mg/dL (RR, 150–250 mg/dL), triglyceride 48 mg/dL (RR, 50–130 mg/dL), free fatty acid 740 µEq/L (RR, 300–480 µEq/L), sodium 135 mEq/L (RR, 136–142 mEq/L), potassium 3.4 mEq/L (RR, 3.8–5.0 mEq/L), phosphorus 6.6 mg/dL (RR, 4.0–7.0 mg/dL), calcium 9.8 mg/dL (RR, 9.0–11.0 mg/dL), magnesium 3.1 mg/dL (RR, 1.3–2.1 mg/dL), blood glucose 14 mg/dL (RR, 70–110 mg/dL), blood ketone negative. Arterial blood gas analysis showed that pH 7.42, pCO
2 29.0 mmHg, HCO
3- 18.5 mmol/L. The level of insulin was 0.2 µIU/mL (RR, 4–24 µIU/mL), cortisol >62.80 µg/dL (RR, 6.7–22.6 µg/dL), ACTH 1,777.0 pg/mL (RR, 7.2–63.3 pg/mL). Blood ammonia was 136 µmol/L (RR, 9–35 µmol/L). Urine organic acid analysis showed that 4-Hydroxypheylacetic acid 73.3 mmol/mol ceatinine (RR, 0.0–69.9 mmol/mol ceatinine). Plasma amino acid analysis revealed no prominent abnormality. Urinalysis showed that ketone 2 positive but no proteinuria or hematuria. Urine microscopy revealed 0–2 /mm
3 white cells and 0–2 /mm
3 red cells. Chest radiography showed no cardiomegaly and no other significant abnormalities. The cerebral spinal fluid (CSF) study showed that white blood cell 0/µL, red blood cell 0–2 /high power field, glucose 27 mg/dL, protein 17.9 mg/dL (RR, 12–60 mg/dL), Herpes simplex type I polymerase chain reaction negative, enterovirus culture negative. The CSF pressure could not be accurately measured. Brain magnetic resonance imaging done on second hospital day showed bilateral symmetrical areas of hyperintensity on diffusion weighted imaging with a low apparent diffusion coefficient value in the thalami, parietal, and temporal lobes, and it was consistent with cytotoxic edema, which can be seen in hypoglycemic encephalopathy (
Fig. 1).
For all the anticonvulsants treatment such as midazolam, phenobarbital and phenytoin, her mentality was stupor and seizures were continued. Intubation and mechanical ventilation was conducted. Despite 10% glucose bolus and continuous infusion at a rate of 15 mg/kg/min with hydrocortisone at a dose of 5 mg/kg/day injection, blood glucose was stabilized above 70 mg/dL after 6 hours from initiation. Empirical L-carnitine solution 55 mg/kg/day divided 3 times was started on the second day. She could be extubated on the third day, but focal seizures developed and progressed. On the fifth day, she was reintubated and midazolam continuous infusion was done. She was seizures-free state on the ninth day, so the anticonvulsants could be tapered but she was kept on phenytoin, phenobarbital, topiramate and oxacarbazepine. Her visual fixation and tracking were disabled. The locomotion and transitional movements such as supine to sit were severely impaired. She was transferred to rehabilitation medicine on the 35th day.
We wonder the etiology of her hypoglycemia because the hospital course was extraordinarily severe and a negative serum ketone was also unusual. A few weeks later, we confirmed the initial serum carnitine level done on the third day was very low (<0.01 µmol/L). We consider primary or secondary carnitine deficiency by other metabolic disorders. The association of exposures to antibiotics containing pivalic acid and hypoglycemia was reported on CDSP. So we conducted gene analysis to confirm CDSP.