Adrenoleukodystrophy (ALD) is an X-linked, metabolic disorder caused by genetic deficiency of peroxisomal ALD protein resulting in accumulation of very-long chain fatty acids (VLCFA) primarily in the adrenal cortex and central nervous system. Approximately 3540% of boys with ALD develop cerebral ALD (CALD), which causes rapidly progressive cerebral demyelination, loss of neurologic function, and death. Disease progress can be halted by allogeneic hematopoietic cell transplantation (HCT), but only if HCT is performed prior to the occurrence of extensive neurologic damage. Radiologic diagnosis of CALD in presymptomatic boys is critical in ensuring early treatment and optimal long-term outcomes. Approximately 85% of boys with ALD present with adrenal insufficiency prior to the onset of neurologic symptoms. Therefore, ALD should be included in the differential diagnosis of boys presenting with adrenal insufficiency without adrenal antibodies. We present the case of a boy who had recurrent episodes of hypoglycaemia starting at age 2. A diagnostic fast showed normal endocrine and metabolic responses to fasting. At 5.5 years, he presented with adrenal insufficiency without adrenal antibodies and commenced hydrocortisone replacement therapy. Subsequent VLCFA analysis demonstrated elevated C26 fatty acids consistent with peroxisomal dysfunction and suggestive of ALD, which was confirmed via molecular genetic analysis of the ABCD1 gene. Apart from a history of temper tantrums, there were no other behavioural or psychological problems. MRI evidence of cerebral involvement emerged at age 7, CALD was suspected, and the child underwent successful unrelated bone marrow transplantation. At last assessment (11.5 years of age), he was performing as expected for age. He is being followed-up for potential endocrine complications of transplantation. Recognition of adrenal insufficiency without adrenal antibodies in this boy prompted VLCFA analysis which identified the underlying diagnosis of ALD. MRI surveillance detected early, pre-symptomatic cerebral disease and permitted a timely bone marrow transplant which successfully arrested cerebral disease progression. Results from a pilot educational program intended to encourage reflex VLCFA testing in cases of negative adrenal antibody lab results suggest that increased awareness of VLCFA test availability doubles the number of patients receiving adrenal antibody and VLCFA tests concurrently. However, reflex testing was not done for most boys, highlighting the continued need for education that adrenal insufficiency in the absence of adrenal antibodies should be a red flag for a potential ALD diagnosis. In patients diagnosed with ALD, ongoing MRI monitoring should be implemented to detect brain changes suggestive of CALD to ensure early treatment.
27 - 29 Sep 2018
European Society for Paediatric Endocrinology