Infantile Refsum Disease

Infantile Refsum disease (IRD), also called infantile phytanic acid storage disease, is a medical condition within the Zellweger spectrum of perixisome biogenesis disorders (PBDs). These inherited genetic disorders damage the white matter of the brain and affect motor movements.

PBDs are part of a larger group of disorders called the leukodystrophies. The Zellweger spectrum of PBDs include related, but not more severe, disorders referred to as Zellweger syndrome (ZS) and neonatal adrenoleukodystrophy.

Collectively, these disorders are caused by inherited defects in any one of 12 genes, called PEX genes, which are required for the normal formation and function of peroxisomes. Peroxisomes are cell structures required for the normal formation and function of the brain, eyes, liver, kidneys, and bone. They contain enzymes that break down toxic substances in the cells, including very long chain fatty acids and phytanic acid (a type of fat found in certain foods), and synthesize certain fatty materials (lipids) that are required for cell function. When peroxisomes are not functioning, there is over-accumulation of very long chain fatty acids and phytanic acid, and a lack of bile acids and plasmalogens–specialized lipids found in cell membranes and the myelin sheaths that encase and protect nerve fibers.

IRD has some residual perixisome function, resulting in less severe disease than in Zellweger syndrome.

Although Adult Refsum disease and IRD have similar names, they are separate disorders caused by different gene defects.

Symptoms of IRD begin in infancy with retinitis pigmentosa, a visual impairment that often leads to blindness, and hearing problems that usually progress to deafness by early childhood. Other symptoms may include:

  • Rapid, jerky eye movements (nystagmus)
  • Floppy muscle tone (hypotonia)
  • Lack of muscle coordination (ataxia)
  • Mental and growth disabilities
  • Abnormal facial features
  • Enlarged liver
  • White matter abnormalities of brain myelin

At the mildest extreme of the disorder, intellect may be preserved.

IRD is a fatal disease, but some children will survive into their teens and twenties, and possibly even beyond.

Currently, there is no cure for infantile Refsum disease syndrome, nor is there a standard course of treatment. Infections should be guarded against to prevent such complications as pneumonia and respiratory distress. They should also avoid foods that contain phytanic acid, including:

  • Dairy products
  • Beef and lamb
  • Fatty fish such as tuna, cod, and haddock

Although this prevents the accumulation of phytanic acid, it does not address the accumulation of very long chain fatty acids, and the deficiency of bile acids and plasmalogens.

Other treatment is symptomatic and supportive. Patients show variable lifespans with some individuals surviving until adulthood and into old age.