[X-linked adrenoleukodystrophy in a female proband: clinical presentation, biological diagnosis and family consequences].
BACKGROUND
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.


METHODS
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.


CONCLUSIONS
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.
Lesca
G
G
Laboratoire de génétique, pavillon E, hôpital Edouard-Herriot, 5, place d'Arsonval, 69437 Lyon cedex 03, France. gaetan.lesca@chu-lyon.fr
Vanier
M T
MT
Creisson
E
E
Bendelac
N
N
Hainque
B
B
Ollagnon-Roman
E
E
Aubourg
P
P
D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D000326:Adrenoleukodystrophy / Q000175:diagnosis* / Q000235:genetics; D000328:Adult; D041322:Chromosomes, Human, Y / Q000235:genetics; D005242:Fecal Incontinence / Q000209:etiology; D005260:Female; D005817:Genetic Counseling; D006801:Humans; D020336:Paraparesis, Spastic / Q000209:etiology; D010375:Pedigree
C115572:ABCD1 protein, human; D000074063:ATP Binding Cassette Transporter, Subfamily D, Member 1; D018528:ATP-Binding Cassette Transporters