A 36-year-old male presented to neurologists with tiredness and clumsy gait. Examination revealed normal cranial nerves, spastic paraparesis and bilateral extensor plantar response, absent vibration sense and ataxia. He was thought to have an inherited form of Spino-Cerebellar ataxia. His mother had developed similar neurological problems in her 50 s, and his maternal uncle had Addisons disease.
He was referred to endocrinologists because of the findings of a low testosterone and slightly enlarged pituitary gland on MR imaging of the brain. Testosterone was low (4.2 nmol/L) and gonadotrophins raised (FSH 19.1, LH 29.2 IU/L). A short synacthen test showed a blunted cortisol response (basal 221, 30 minutes 236 nmol/L). ACTH was raised (182 pg/ml). Renin, aldosterone levels were normal. Very long chain fatty acid (VLCFA) measurements were abnormal: C26 fatty acid levels were high (6.78, NR: 0.34.0 umol/l), and C24/C22 and C26/C22 ratios were raised.
These results suggest a diagnosis of adult-onset myeloneuropathy variety of adrenoleukodystrophy (ALD). This is supported by the family history of an X-linked inheritance and finding the gene defect in ABCD1 gene in the patient.
ALD, an X-linked recessive disorder, is caused by mutations in the ABCD1 gene (Chromosome Xq28) which encodes a peroxisomal membrane protein of the ATP-binding cassette transporter family. This protein transports VLCFAs across the peroxisomal membrane. In ALD, the VLCFA Co A synthetase in peroxisomes are therefore unable to breakdown VLCFAs which accumulate as cytoplasmic inclusions leading to progressive dysfunction in the nervous system, adrenal glands and testes.
Our patient had developed neurological and endocrine manifestations, notably adrenal insufficiency and primary gonadal failure and is being treated with hydrocortisone and testosterone.
01 - 05 Apr 2006
European Society of Endocrinology