A First Case of Adrenomyeloneuropathy With Mutation Y174S of the Adrenoleukodystrophy Gene

Neuro Endocrinol Lett. 2017 Feb;38(1):13-18.

Abstract

The patient first noticed spasticity and weakness in his legs. He was diagnosed with chronic myelogenous leukemia (CML); the symptoms were attributed to neuropathy associated with CML. By treatment with dasatinib, he achieved complete hematological remission, but his difficulty in walking was not improved. His neurological symptom worsened together with an increase in body temperature and then disappeared together with a normalized body temperature, which may be attributed to the Uhthoff's phenomenon often observed in multiple sclerosis. He later developed acute fever, vomiting and a high adrenocorticotropic hormone (ACTH) level, which was diagnosed as adrenal insufficiency. Eventually, he was diagnosed with a milder form of adrenoleukodystrophy (ALD), adrenomyeloneuropathy (AMN) by increased levels of Very Long Chain Fatty Acids (VLCFAs) and genetic testing of the ATP binding cassette subfamily D member 1 (ABCD1) gene. A missense mutation (c.521A>C, p.Tyr174Ser), previously reported to induce severe cerebral ALD, was detected in exon1. Thus, clinical manifestation of ALD is determined by interaction between the primary ABCD1 mutation and modifying genetic and environmental factors. Physicians should be aware of the differing symptoms of AMN and determine the level of VLCFAs in patients having primary adrenal insufficiency, especially those complicated with neurological dysfunction. This is the first report of an AMN patient complicated with CML.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics*
  • Adrenal Insufficiency / diagnosis
  • Adrenal Insufficiency / etiology*
  • Adrenal Insufficiency / genetics
  • Adrenal Insufficiency / metabolism
  • Adrenoleukodystrophy / complications*
  • Adrenoleukodystrophy / diagnosis
  • Adrenoleukodystrophy / genetics
  • Adrenoleukodystrophy / metabolism
  • Antineoplastic Agents / therapeutic use
  • Brain / diagnostic imaging
  • Dasatinib / therapeutic use
  • Fatty Acids / metabolism
  • Gene-Environment Interaction
  • Humans
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / complications*
  • Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense*
  • Young Adult

Substances

  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters
  • Antineoplastic Agents
  • Fatty Acids
  • Dasatinib