[X-linked Adrenoleukodystrophy in a Female Proband: Clinical Presentation, Biological Diagnosis and Family Consequences]

Arch Pediatr. 2005 Aug;12(8):1237-40. doi: 10.1016/j.arcped.2005.03.050.
[Article in French]

Abstract

Introduction: X-linked adrenoleukodystrophy (ALD) is the most frequent type of leukodystrophy (1/17 000 males). The phenotypic range in male patients varies from the severe cerebral presentations in children to the milder myeloneuropathy and to isolate adrenal insufficiency. More than a half of the carrier females display clinical symptoms over the age of 40 years.

Observation: Diagnosis of ALD was raised in a 40 year-old female who presented with spastic paraparesis and sphincterian dysfunction, occurring after the delivery of her first child. There was no family history of ALD. Very long-chain fatty acids (VLFCA) were assayed in her one-year-old son in order to propose appropriate hormonal and neurological survey. His dosage was abnormal and an adrenal insufficiency was subsequently found. A brain MRI will be proposed biannually when he reaches to age of for years. The proband's mother had an increased level of VLCFA, showing that she was a carrier. Family screening was extended to the proband's sisters and maternal aunt who already had children, but also to her brother, who may express a mild form of the disease later on, and to her maternal uncles who might be asymptomatic carriers. A frameshift mutation was found in the ABCD1 gene and will allow accurate carrier identification and prenatal diagnosis in the family.

Conclusion: ALD diagnosis should be evoked in a woman affected by myelopathy despite the lack of family history. Such a diagnosis has severe consequences since some of the related males may carry the mutation although they do not display any symptom at time of diagnosis, and because carrier females have a risk to both have a clinical expression of the disease and give birth to an affected boy.

Publication types

  • Case Reports

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters / genetics
  • Adrenoleukodystrophy / diagnosis*
  • Adrenoleukodystrophy / genetics
  • Adult
  • Chromosomes, Human, Y / genetics
  • Fecal Incontinence / etiology
  • Female
  • Genetic Counseling
  • Humans
  • Paraparesis, Spastic / etiology
  • Pedigree

Substances

  • ABCD1 protein, human
  • ATP Binding Cassette Transporter, Subfamily D, Member 1
  • ATP-Binding Cassette Transporters