Rare Diseases Symptoms Automatic Extraction

Mitochondrial dysfunction and oxidative damage cooperatively fuel axonal degeneration in X-linked adrenoleukodystrophy.


X-linked adrenoleukodystrophy (X-ALD) is the most frequent inherited monogenic demyelinating disease (minimal incidence 1:17,000). It is often lethal and currently lacks a satisfactory therapy. The disease is caused by loss of function of the ABCD1 gene, a peroxisomal ATP-binding cassette transporter, resulting in the accumulation of VLCFA (very long-chain fatty acids) in organs and plasma. Understanding of the aetiopathogenesis is a prerequisite for the development of novel therapeutic strategies. Functional genomics analysis of an ABCD1 null mouse, a mouse model for adrenomyeloneuropathy, has revealed presymptomatic alterations in several metabolic pathways converging on redox and bioenergetic homeostasis, with failure of mitochondrial OXPHOS disruption and mitochondrial depletion. These defects could be major contributors to the neurodegenerative cascade, as has been reported in several neurodegenerative disorders. Drugs targeting the redox imbalance/mitochondria dysfunction interplay have shown efficacy at halting axonal degeneration and associated disability in the mouse, and thus offer therapeutic hope.

Diseases presenting "loss of function" symptom

  • adrenomyeloneuropathy
  • benign recurrent intrahepatic cholestasis
  • cadasil
  • canavan disease
  • congenital adrenal hyperplasia
  • cystinuria
  • familial hypocalciuric hypercalcemia
  • gm1 gangliosidosis
  • harlequin ichthyosis
  • hirschsprung disease
  • holt-oram syndrome
  • kabuki syndrome
  • kallmann syndrome
  • krabbe disease
  • lamellar ichthyosis
  • papillon-lefèvre syndrome
  • pendred syndrome
  • triple a syndrome
  • trochlear dysplasia
  • x-linked adrenoleukodystrophy

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