According to Charcot-Marie-Tooth News, researchers have associated HINT1 gene mutations with neuropathy in Greek patients with Charcot-Marie-Tooth disease (CMT). In the past, HINT1 was linked to CMT in central and southeastern Europe. However, researchers questioned whether the same gene mutation was widely found in Greek patients with CMT and, if so, how the mutation affected them. Within this particular study, researchers determined that autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) caused by HINT1, which exists on the same spectrum as CMT, was just as common in Greece as it was in other countries.
Interested in learning more? Take a look at the study findings in the Journal of the Peripheral Nervous System.
Neuropathy with Neuromyotonia
To begin, let’s explore what autosomal recessive axonal neuropathy with neuromyotonia (ARAN-NM) is. According to MedLine Plus, ARAN-AM is:
a disorder that affects the peripheral nerves, [which] connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound. In people with autosomal recessive axonal neuropathy with neuromyotonia, the damage primarily causes progressive weakness and wasting (atrophy) of muscles in the feet, legs, and hands.
Additional symptoms include exercise intolerance, an abnormal gait, joint contractors in the hands and feet, and neuromyotonia. Neuromyotonia occurs when peripheral nerves become over-activated, stopping results from relaxing following contraction, cramping, and involuntary muscle rippling. Because it is inherited in an autosomal recessive pattern, patients must inherit one defective gene from each parent. Previously, HINT1 was discovered to cause ARAN-AM. Normally, the gene plays a role in cell signaling. Without the genes, the peripheral nerves begin wasting and twitching; have trouble relaxing; and often cramp.
Researchers wanted to explore how common this was in Greece. First, they sourced DNA from 42 separate patients: 36 (85.7%) with CMT2 and 6 (14.3%) with distal hereditary motor neuropathy. Researchers discovered four patients with balletic biallelic gene mutations. Although the patients made up a small sample of the chosen group, they also made up 44.4% of those experiencing neuromyotonia. For all four patients, symptom onset appeared between ages 8-15.
After exploring HINT1 mutations from patients in other countries, researchers determined that there was a similar prevalence of axonal neuropathy with neuromyotonia between those patients and the Greek patients. Therefore, the researchers recommend that any patients who are suspected of ARAN-AM should undergo testing for the relevant HINT1 variant.
Charcot-Marie-Tooth Disease (CMT)
A variety of gene mutations are associated with Charcot-Marie-Tooth disease (CMT), a rare but most commonly inherited neurological disorder. Also known as hereditary motor and sensory neuropathy, CMT causes peripheral nerve damage and degeneration. As this damage progresses, nerves and muscles are unable to properly communicate. Symptoms of CMT usually manifest in adolescence or early adulthood, though symptoms may appear in later years. These include:
- Foot deformities (high arches, hammertoes)
- Frequent tripping or falling
- Foot drop
- Muscle atrophy and weakness in the hands
- Foot and lower leg muscle weakness
- Difficulty walking
- “Pins and needles” sensation
