What Is HMSN-4?
HMSN-4 is a type of CMT caused by autosomal recessive mutations in the PHYH gene. This gene provides instructions for making the enzyme phytanoyl-CoA hydroxylase, which breaks down phytanic acid, a fatty acid obtained from the diet. Mutations in the PHYH gene disrupt this function, leading to impaired nerve signal transmission.
HMSN-4 is autosomal recessive, meaning that both copies of the gene must have a mutation to cause this subtype.
Clinical Features
HMSN-4, also known as Refsum disease, is a metabolic disease caused by the buildup of phytanic acid, a fatty acid the body normally breaks down. Symptoms usually begin in childhood or adolescence and affect multiple systems in addition to the peripheral nerves. Nerve conduction studies reflect an axonal and demyelinating process.
HMSN-4 symptoms may include:
- Progressive vision loss from retinitis pigmentosa
- Reduced sense of smell (anosmia)
- Peripheral neuropathy with weakness and reduced sensation
- Poor balance and coordination (ataxia)
- Hearing loss
- Dry, scaly skin
- Foot drop
- Additional symptoms not listed here
Disease Course
HMSN-4 shows variability in severity and progression. Because the disease is driven by dietary phytanic acid, dietary management can slow or stabilize progression in some individuals. Disease progression is generally slow, though episodes may occur.
