Background: X-Linked Adrenoleucodystrophy (X-ALD) is a rare neurodegenerative disorder characterised by impaired peroxisomal beta-oxidation of very long chain fatty acids (VLCFA; ≧C22) which is reduced to about 30% of control levels. Consequently, there is an accumulation of VLCFA in plasma and tissues, including the white matter of the brain, the spinal cord and adrenal cortex. It is caused by mutation in the ABCD1 gene encoding a peroxisomal transmembrane protein (ALDP) with the structure of an half ATP-binding cassette transporter. The clinical spectrum in males ranges from isolated adrenal insufficiency and slowly progressive mieloneuropathy to devastating cerebral demielination.
Case presentation: An 4.8 year-old boy born to non-consanguineous parents was referred to our clinic because of oral melanosis (Peutz-Jeghers syndrome suspicion). Family history was unremarkable. Past medical history was positive for febrile seizures at age 2 and 3. On physical/neurological examination, only cutaneous-mucosal hyperpigmentation was noted. Growth was normal (height 112 cm, weight 18 kg, head circumference 50 cm). Serum cortisol (F<10 μg/l) and ACTH concentrations (ACTH>1250 pg/ml) were compatible with Addisons disease. Adrenal autoantibodies were negative, as well as molecular analyses of AIRE, DAX1, AAAS, MC2R and MRAP genes. The elevated plasma concentrations of VLCFA (C26:0=4.260 umol/, range 0.4600.980; C26:0/C22:0=0.094, range<0.096; C24:0/C22:0=1.66, range<1.01) and the following molecular analysis with sequencing of ABCD1 gene established the diagnosis of X-ALD. Brain MRI and neurophysiological studies were normal. In addition to glucocorticoid therapy, the patient initiated restriction of VLCFA by reducing the intake of fatty foods.
Conclusion: Addisons disease can be the presenting symptom of X-ALD, years before the onset of neurological symptoms. Because of the prognostic implications, the need for genetic counselling and the potential benefit of therapeutic intervention, such patients need to be identified promptly. Accordingly, we suggest that any boy with Addisons disease (in particular when circulating adrenal autoantibodies are absent) should be tested for X-ALD.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology