Encyclopedia
Autosomal recessive axonal neuropathy with neuromyotonia is a disorder that affects the peripheral nerves. Peripheral nerves connect the brain and spinal cord to muscles and to sensory cells that detect sensations such as touch, pain, heat, and sound.
- genetic conditions
1. Introduction
Axonal neuropathy, a characteristic feature of this condition, is caused by damage to a particular part of peripheral nerves called axons, which are the extensions of nerve cells (neurons) that transmit nerve impulses. 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. Muscle weakness may be especially apparent during exercise (exercise intolerance) and can lead to an unusual walking style (gait), frequent falls, and joint deformities (contractures) in the hands and feet. In some affected individuals, axonal neuropathy also causes decreased sensitivity to touch, heat, or cold, particularly in the lower arms or legs.
Another feature of this condition is neuromyotonia (also known as Isaac syndrome). Neuromyotonia results from overactivation (hyperexcitability) of peripheral nerves, which leads to delayed relaxation of muscles after voluntary tensing (contraction), muscle cramps, and involuntary rippling movement of the muscles (myokymia).
2. Frequency
Autosomal recessive axonal neuropathy with neuromyotonia is a rare form of inherited peripheral neuropathy. This group of conditions affects an estimated 1 in 2,500 people. The prevalence of autosomal recessive axonal neuropathy with neuromyotonia is unknown.
3. Causes
Autosomal recessive axonal neuropathy with neuromyotonia is caused by mutations in the HINT1 gene. This gene provides instructions for making a protein that is involved in the function of the nervous system; however its specific role is not well understood. Laboratory studies show that the HINT1 protein has the ability to carry out a chemical reaction called hydrolysis that breaks down certain molecules; however, it is not known what effects the reaction has in the body.
HINT1 gene mutations that cause autosomal recessive axonal neuropathy with neuromyotonia lead to production of a HINT1 protein with little or no function. Sometimes the abnormal protein is broken down prematurely. Researchers are working to determine how loss of functional HINT1 protein affects the peripheral nerves and leads to the signs and symptoms of this condition.
4. Inheritance
This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
5. Other Names for This Condition
- autosomal recessive Charcot-Marie-Tooth disease type 2 with neuromyotonia
- autosomal recessive neuromyotonia and axonal neuropathy
- Gamstorp-Wohlfart syndrome
- myokymia, myotonia, and muscle wasting
- NMAN
- Autosomal recessive axonal neuropathy with neuromyotonia
This entry is adapted from the peer-reviewed paper https://medlineplus.gov/genetics/condition/autosomal-recessive-axonal-neuropathy-with-neuromyotonia
References
- Caetano JS, Costa C, Baets J, Zimon Phd M, Venâncio Phd M, Saraiva Phd J,Negrão L, Fineza I. Autosomal recessive axonal neuropathy with neuromyotonia: arare entity. Pediatr Neurol. 2014 Jan;50(1):104-7. doi:10.1016/j.pediatrneurol.2013.08.028.
- Zhao H, Race V, Matthijs G, De Jonghe P, Robberecht W, Lambrechts D, Van DammeP. Exome sequencing reveals HINT1 mutations as a cause of distal hereditary motorneuropathy. Eur J Hum Genet. 2014 Jun;22(6):847-50. doi: 10.1038/ejhg.2013.231.
- Zhou X, Chou TF, Aubol BE, Park CJ, Wolfenden R, Adams J, Wagner CR. Kineticmechanism of human histidine triad nucleotide binding protein 1. Biochemistry.2013 May 21;52(20):3588-600. doi: 10.1021/bi301616c.
- Zimoń M, Baets J, Almeida-Souza L, De Vriendt E, Nikodinovic J, Parman Y,Battaloğlu E, Matur Z, Guergueltcheva V, Tournev I, Auer-Grumbach M, De Rijk P,Petersen BS, Müller T, Fransen E, Van Damme P, Löscher WN, Barišić N, Mitrovic Z,Previtali SC, Topaloğlu H, Bernert G, Beleza-Meireles A, Todorovic S,Savic-Pavicevic D, Ishpekova B, Lechner S, Peeters K, Ooms T, Hahn AF, Züchner S,Timmerman V, Van Dijck P, Rasic VM, Janecke AR, De Jonghe P, Jordanova A.Loss-of-function mutations in HINT1 cause axonal neuropathy with neuromyotonia.Nat Genet. 2012 Oct;44(10):1080-3. doi: 10.1038/ng.2406.
