H-ABC

Hypomyelinating Leukodystrophy With Atrophy of the Basal Ganglia and Cerebellum (H-ABC; HLD6) and Autosomal Dominant Torsion Dystonia 4 (DYT4)

Gene: TUBB4A (also known as TUBB4, TUBB5)

Protein: tubulin, beta 4

Clinical Characteristics

H-ABC

  • Also known as hypomyelinating leukodystrophy 6
  • Infancy to early childhood onset
  • Developmental delay
  • Progressive deterioration of motor skills
  • Extrapyramidal movement disorders:
    • Dystonia
    • Choreoathetosis
    • Rigidity
    • Opisthotonus
    • Oculogyric crises
  • Progressive spastic tetraplegia
  • Ataxia
  • Cognition relatively preserved
  • MRI features:
    • Hypomyelination
    • Cerebellar atrophy
    • Absence or disappearance of putamen

DYT4

  • Onset in second to fourth decade
  • Progressive spasmodic “whispering” dysphonia
  • Cervical or generalized dystonia
  • Characteristic “hobby horse” gait ataxia
  • Normal MRI

Inheritance pattern: Autosomal dominant or sporadic

What Can Be Learned From This Test

Testing is performed by sequencing the entire coding region of the TUBB4A gene. This will detect point mutations, small deletions and small insertions. It will not detect a partial or whole gene deletion or duplication.

Targeted mutation analysis for the common mutations c.745G>A; p.Asp249Asn in H-ABC or c.4C>G; p.Arg2Gly in DYT4 can be carried out. Please note on submission form if this targeted approach is being requested.

A negative test result does not rule out a genetic cause of hypomyelinating leukodystrophy, since there are many other genes associated with leukodystrophies, some of which are available for testing in our laboratory. 

Sample Requirements

Draw 2ml–4ml of blood in EDTA/purple-top tube (minimum of 1ml–2ml for infants).

Turnaround time: 7-10 business days

CPT Codes and Cost

H-ABC Common Mutation Testing

  • Code: 81479
  • Cost: $225

Full Gene Sequencing

  • Code: 81479
  • Cost: $500

DYT4 Common Variant Testing

  • Code: 81479
  • Cost: $225

Known Variant Testing

  • Code: 81479
  • Cost: $225

Additional Information