Adrenoleukodystrophy: a trap for the physician
Authors: Azam SN , Beadsworth MBJ , Jenkins NE , Beeching NJ , Nye FJ , Evans J 
Published: May 2014

A 40-year-old man presented to the accident and emergency department having suffering a generalized tonic-clonic seizure. Despite intravenous diazepam and phenytoin he continued to have focal seizures. His Glasgow Coma Scale fluctuated between 6 and 11 out of 15, he was haemodynamically stable and, apart from focal seizures, systemic examination was unremarkable.Investigations revealed a mild leucocytosis. Biochemical parameters (urea and electrolytes, liver function tests including gamma glutamyl transferase) were within normal range. A computed tomography scan of the brain showed generalized white matter changes (low attenuation) particularly in the frontal lobes. The patient was sedated, ventilated and transferred to the intensive therapy unit.Initial history from relatives suggested that he suffered with Addison's disease and was on replacement hydrocortisone and fludrocortisone for this. His former partner claimed alcohol abuse and behavioural problems, which had worsened recently. He had suffered a head injury a few months earlier but had been discharged within 24 hours as observations had remained stable. There was no other significant past medical history.It transpired that his alcohol intake was moderate. At the time of his admission there was an outbreak of echo 30 virus meningoencephalitis in Merseyside. His presentation with confusion, fluctuating levels of conscious and seizures led to a working diagnosis of encephalitis and aciclovir was commenced. Differential diagnoses included alcohol excess or withdrawal fits and stimulant drug overdose. A toxicology screen was negative and no alcohol was detected in the blood.A diagnostic lumbar puncture showed clear and colourless CSF with glucose 2.8 mmol/litre (blood glucose 4.6 mmol/litre), protein 0.91 g/litre (normal 0.15–0.4 g/litre), red blood cell count 2×106/litre, white blood cell count <1×106/litre, with no organisms seen on microscopy and no growth on cultures. CSF polymerase chain reaction tests for meningococcus, herpes simplex virus and enterovirus (including echovirus) were negative. Blood, urine, throat swab and sputum cultures showed no growth. Human immunodeficiency virus 1 and 2 antibodies were not detected.Following successful extubation he was transferred to the infectious diseases unit but behavioural problems persisted. A more extensive history revealed multiple family episodes of Addison's disease, all four of his male siblings having been diagnosed, two of whom had died as young children. His sister's son also suffered from Addison's disease, suggesting a pattern of recessive X-linked inheritance. A magnetic resonance scan of the brain was performed. This revealed high intensity signal changes in the periventricular white matter, sparing the basal ganglia and most marked in the frontal and occipital areas (Figure 1). This appearance could be seen in inflammatory, ischaemic, neoplastic or degenerative processes, but the distribution was more suggestive of a white matter degenerative disease.Adrenoleukodystrophy was suggested to account for hypoadrenalism, white matter changes and the suggested inheritance pattern. Further information from his family revealed that he had undergone tests for an inherited disorder 10 years earlier but there was no ongoing follow up.An assay of very long chain fatty acids and genetic studies were requested. However, recovery of old notes confirmed that these tests had indeed been previously undertaken and that the patient was already diagnosed with X-linked adrenoleukodystrophy. Seizure free, but with some behavioural and cognitive dysfunction, he was discharged with neurological follow up arranged.