X-linked adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disease characterized by Progressive demyelinisation of the central nervous system (CNS) (brain and/or Spinal cord) and Peripheral adrenal insufficiency. The Cerebral forms of Juvenile X-ALD (45% of the cases) affect previously healthy 5 to 12 year-old boys. The adult form, adrenomyeloneuropathy (AMN), is characterized by the onset of Spastic paraparesia between 20 and 45 years of age, associated with gait disturbances, urinary Disorders and Sexual dysfunction.

Additional Information

X-linked adrenoleukodystrophy (X-ALD) is characterized by Progressive demyelinisation of the central nervous system (CNS) (brain and/or Spinal cord) and Peripheral adrenal insufficiency. The incidence is 1/17,000 births, including hemizygotes and heterozygous Women who very often present with symptoms. Prevalence is estimated at 1/20,000. The Cerebral forms of Juvenile X-ALD (45% of the cases) affect previously healthy 5 to 12 year-old boys. The first manifestations are moderate Cognitive deficits, followed by Progressive demyelinisation of the central nervous system, with diminished visual acuity, central deafness, Cerebellar ataxia, hemiplegia, convulsions and Dementia leading to a neurovegetative state or Death within several years. The adult form, adrenomyeloneuropathy (AMN), is characterized by the onset of Spastic paraparesia between 20 and 45 years of age, associated with gait disturbances, urinary Disorders and Sexual dysfunction. The disease progresses towards severe paraplegia complicated by Cerebral demyelinisation in 30% of cases. Transmission is X-linked recessive, except for 8% of de novo mutations. More than 471 different mutations of the ABCD1 Gene have been described. Tissue build-up of very long chain fatty acids (VLCFA) has been observed, but its toxicity failed to be demonstrated. Clinical Diagnosis is confirmed by the demonstration of High concentrations of VLCFA in plasma or fibroblasts. Screening of heterozygous Women is based on the measurement of VLCFA concentrations in plasma (95% reliability), the study of the X-ALD protein in fibroblasts or monocytes/lymphocytes and the search for the ABCD1 Gene mutation. Genetic counselling is used to identify Women at risk of being carriers, boys not yet presenting with neurological symptoms (in order to provide early therapy), and ALD patients with adrenal insufficiency, as it can be life-threatening in absence of any treatment. Prenatal Diagnosis can be performed (after chorionic villus sample at 10-12 weeks of gestation). Allogeneic bone-marrow transplantation, when performed at an early stage of the disease, can stabilize and even reverse Cerebral demyelinisation in boys with the Cerebral form. Two Young patients have received, as part of a gene Therapy trial, autologous bone-marrow transplants, genetically corrected ex vivo. The results, so far (6 months and one year postoperative), are promising. Neuroprotective treatments for AMN are currently being studied. Lorenzo's oil (mix of unsaturated long chain fatty acids) could reduce the risk of Brain damage, when given before the age of six.

Also Known As

  • Schilder-Addison complex
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