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GTR Home > Tests > very long chain fatty acids (cultured cells)

Indication

This is a clinical test intended for Help: Diagnosis, Mutation Confirmation

Clinical summary

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Imported from GeneReviews

X-linked adrenoleukodystrophy (X-ALD) affects the nervous system white matter and the adrenal cortex. Three main phenotypes are seen in affected males: The childhood cerebral form manifests most commonly between ages four and eight years. It initially resembles attention-deficit disorder or hyperactivity; progressive impairment of cognition, behavior, vision, hearing, and motor function follow the initial symptoms and often lead to total disability within six months to two years. Most individuals have impaired adrenocortical function at the time that neurologic disturbances are first noted. Adrenomyeloneuropathy (AMN) manifests most commonly in an individual in his twenties or middle age as progressive stiffness and weakness of the legs, sphincter disturbances, sexual dysfunction, and often, impaired adrenocortical function; all symptoms are progressive over decades. "Addison disease only" presents with primary adrenocortical insufficiency between age two years and adulthood and most commonly by age 7.5 years, without evidence of neurologic abnormality; however, some degree of neurologic disability (most commonly AMN) usually develops by middle age. More than 20% of female carriers develop mild-to-moderate spastic paraparesis in middle age or later. Adrenal function is usually normal.

Clinical features

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Imported from Human Phenotype Ontology (HPO)

  • Alopecia
  • Bowel incontinence
  • Hypogonadism
  • Neurodegeneration
  • Psychotic disorder
  • Seizure
  • Spastic paraplegia
  • Urinary incontinence
  • Polyneuropathy
  • Hyperpigmentation of the skin
  • Paraparesis
  • Atypical behavior
  • Slurred speech
  • Mental deterioration
  • Truncal ataxia
  • Blindness
  • Dementia
  • Incoordination
  • Loss of speech
  • Limb ataxia
  • Abnormal cerebral white matter morphology
  • Attention deficit hyperactivity disorder
  • Hearing impairment
  • Lower limb muscle weakness
  • Urinary bladder sphincter dysfunction
  • Impaired vibration sensation at ankles
  • Elevated circulating long chain fatty acid concentration
  • Visual loss
  • Primary adrenal insufficiency
  • Bulbar palsy
  • Impotence
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Inheritance pattern

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X-linked inheritance

Conditions tested

Disease mechanism

loss of function

Target population

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X-linked adrenoleukodystrophy, peroxisomal biogenesis disorders (Zellweger spectrum disorders), peroxisomal D-Bifunctional enzyme deficiency, and peroxisomal acyl-CoA- oxidase deficiency.

Citations

  • Moser HW, 2005. Lysosomal and peroxisomal diseases. In: Basic Neurochemistry: Molecular, Cellular, and Medical Aspects. Seigel GJ, Albers W, Brady ST, Price DL (Eds). Elsevier Academic Press, San Diego. Seventh Edition. Chapter 41, pp. 685-694.

Clinical validity

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Abnormal results are associated with a disorder of peroxisomal fatty acid oxidation. The PDL laboratory currently has data on more than 200 control cell lines, more than 50 cell lines from X-linked adrenoleukodystrophy males, mutation proven heterozygotes for ALD, peroxisomal biogenesis disorders, and the single enzyme defects of peroxisomal fatty acid oxidation, D-bifunctional and Acyl-CoA oxidase.

Citations
  • X-linked adrenoleukodystrophy. - PubMed ID: 17342190
  • Peroxisomal disorders: complementation analysis using beta-oxidation of very long chain fatty acids. - PubMed ID: 2222480
  • Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups. - PubMed ID: 7541833
  • Moser HW, and Moser AB, 1991. Measurement of saturated very long chain fatty acids in plasma. In Techniques in Diagnostic Human Biochemical Genetics. Hommes FA (Ed). New York: Wiley-Liss. Chapter 12, pp. 177-191.

Clinical utility

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Establish or confirm diagnosis

Citations
  • X-linked adrenoleukodystrophy. - PubMed ID: 17342190
  • Peroxisomal disorders: complementation analysis using beta-oxidation of very long chain fatty acids. - PubMed ID: 2222480
  • Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups. - PubMed ID: 7541833

Guidance for management

Citations
  • Adrenoleukodystrophy: new approaches to a neurodegenerative disease. - PubMed ID: 16380594
  • X-linked adrenoleukodystrophy. - PubMed ID: 17342190
  • Peroxisomal disorders: complementation analysis using beta-oxidation of very long chain fatty acids. - PubMed ID: 2222480
  • Phenotype of patients with peroxisomal disorders subdivided into sixteen complementation groups. - PubMed ID: 7541833

Practice guidelines

  • ACMG ACT, 2023
    American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Elevated lysophosphatidylcholines, X-Linked Adrenoleukodystrophy (X-ALD), 2023
  • ACMG Algorithm, 2023
    ACMG Algorithm, X-ALD: Elevated lysophosphatidylcholines C24:0, C26:0, 2023
  • AAP, 2021
    Leukodystrophies in Children: Diagnosis, Care, and Treatment, Pediatrics (2021) 148 (3): e2021053126.
  • EuroGentest, 2011
    Clinical utility gene card for: adrenoleukodystrophy.

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