Rare Diseases Symptoms Automatic Extraction

Loss of AMP-activated protein kinase in X-linked adrenoleukodystrophy patient-derived fibroblasts and lymphocytes.

[adrenomyeloneuropathy]

X-Adrenoleukodystrophy (X-ALD) is a peroxisomal disorder characterized by accumulation of very-long-chain (VLC) fatty acids, which induces inflammatory disease and alterations in cellular redox, both of which are reported to play a role in the pathogenesis of the severe form of the disease (childhood cerebral ALD). While the mutation defect in ABCD1 gene is common to all forms of X-ALD it fails to account for the spectrum of phenotypic variability seen in X-ALD patients, strongly suggesting a role for as yet unidentified modifier gene(s). Here we report, for the first time, loss of AMP-activated protein kinase alpha1 (AMPKα1) in patient-derived fibroblasts and lymphocytes of the severe cerebral form of X-ALD (ALD), and not in the milder adrenomyeloneuropathy (AMN) form. Decrease in AMPK was observed at both protein and mRNA levels. AMPK loss in ALD patient-derived fibroblasts was associated with increased ubiquitination. Using the Seahorse Bioscience XF(e)96 Flux Analyzer for measuring the mitochondrial oxygen consumption and extracellular acidification rate we show that ALD patient-derived fibroblasts have a significantly lower "metabolic state" than AMN fibroblasts. Unstimulated ALD patient-derived lymphocytes had significantly higher proinflammatory gene expression. Selective AMPK loss represents a novel physiopathogenic factor in X-ALD disease mechanism. Strategies aimed at upregulating/recovering AMPK levels might have beneficial therapeutic effects in X-ALD.

Diseases presenting "first time" symptom

  • achondroplasia
  • acute rheumatic fever
  • adrenal incidentaloma
  • adrenomyeloneuropathy
  • alpha-thalassemia
  • aniridia
  • aromatase deficiency
  • canavan disease
  • carcinoma of the gallbladder
  • cholangiocarcinoma
  • classical phenylketonuria
  • congenital adrenal hyperplasia
  • congenital toxoplasmosis
  • cowden syndrome
  • cushing syndrome
  • cutaneous mastocytosis
  • dedifferentiated liposarcoma
  • dentin dysplasia
  • dentinogenesis imperfecta
  • dracunculiasis
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • erdheim-chester disease
  • erythropoietic protoporphyria
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • esophageal squamous cell carcinoma
  • fabry disease
  • familial mediterranean fever
  • gm1 gangliosidosis
  • harlequin ichthyosis
  • heparin-induced thrombocytopenia
  • hirschsprung disease
  • hodgkin lymphoma, classical
  • holt-oram syndrome
  • hydrocephalus with stenosis of the aqueduct of sylvius
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • kallmann syndrome
  • liposarcoma
  • locked-in syndrome
  • lymphangioleiomyomatosis
  • malignant atrophic papulosis
  • megacystis-microcolon-intestinal hypoperistalsis syndrome
  • monosomy 21
  • neuralgic amyotrophy
  • oculocutaneous albinism
  • oligodontia
  • omenn syndrome
  • oral submucous fibrosis
  • papillon-lefèvre syndrome
  • pendred syndrome
  • phenylketonuria
  • primary effusion lymphoma
  • primary hyperoxaluria type 1
  • severe combined immunodeficiency
  • sneddon syndrome
  • triple a syndrome
  • trochlear dysplasia
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wiskott-aldrich syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy
  • zellweger syndrome

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