Symptom Evolution

Of the sisters diagnosed by Optiz (mentioned above), the first sister died at one year of age of respiratory failure, after suffering progressive weakness and respiratory insufficiency over many months. The second sister developed seizures around four months of age. She was given treatment with L-dopa/carbidopa and BH4 (tetrahydrobiopterin) for low cerebrospinal fluid levels of BH4 and HVA (a dopamine metabolite) and had some clinical response characterized by improved ptosis, level of alertness and circulatory instability. However, she continued to decline over time, and ultimately died at 19 months of age with acute respiratory distress syndrome in association with an influenza infection. Identification of similarly affected infants could help to further clarify the genetic and pathophysiologic basis of this disorder.

Diagnostic Studies

The following are some diagnostic studies we conduct and the characteristics they reveal. Brain MRI indicates a diffuse decrease in myelin (white matter) but also widespread brain atrophy (loss of nerve cell bodies or grey matter). Decreased myelin formation and evidence of progressive myelin loss occurs over time (myelin, or white matter, is the substance that surrounds nerve cells and helps them conduct electrical signals faster and more efficiently; one general term for brain disorders that involve these kind of changes is leukodystrophy).

  • EMG (electromyography: a special test used to help determine the cause of the weakness) shows that the weakness is most consistent with anterior horn cell disease or a motor predominant neuronopathy. Anterior horn cells are the cells in the spinal cord that send out the nerve fibers to the muscles to make them work properly.
  • Muscle and nerve biopsy studies reveal findings indistinguishable from those seen in 5q SMA: neurogenic atrophy.
  • Metabolic evaluation excluded hexosaminidase deficiency, serine deficiency, peroxisomal and mitochondrial dysfunction.
  • Cerebrospinal fluid analysis (CSF) for neurotransmitter metabolites in one sibling revealed evidence of tetrahydrobiopterin (BH4) deficiency and decreased homovanillic acid (HVA) consistent with a central nervous system dopamine deficiency state. It is unclear whether these abnormalities are primary or secondary.

Please contact our clinical coordinators at 801-585-9717 if your child is similarly affected, to inquire about participating in research studies to help us better understand this complex disorder.