Agel amyloidosis ICD-10: E85.1; ICD-11: 5D00.2Y

Hereditary gelsolin amyloidosis (AGel), also called Meretoja syndrome, is a rare, dominantly inherited systemic amyloidosis that results in damage primarily to the eyes, nerves, and skin. The disease is caused by the deposition of gelsolin amyloid fibrils. The cause is a mutation in the Gelsolin gene(GSN gene), which leads to instability of the protein Gelsolin. The protein Gelsolin is an actin modulating protein that plays a role especially in the nervous system. The mutation leads to the deposition of misfolded fibrils of the protein formed and damage to the eyes, nerves and skin.

AGel is an autosomal dominantly inherited genetic disease. Several mutations of gelsolin have been described as causative, the most common (c.640G >A) being observed particularly in Finland (Finnish AGel) with a penetrance of 100% (all patients with the mutation also develop symptoms during their lifetime). AGel accumulates extracellularly in many tissues and along elastic fibers. AGel deposition is associated with degradation of elastic fibers and leads to severe clinical manifestations such as cutis laxa and angiopathic complications.

Symptoms appear between the ages of 40-50 years.

Eyes: almost all patients suffer from dry eyes, in many patients vision deteriorates over time due to the deposition of gelsolin amyloid in the cornea (lattice corneal atrophy). This mainly affects the center of the visual field, the edges are often left out. About 50% of patients also suffer from cataract, and some from glaucoma.

Nerves: Two-thirds of patients have paralysis of the facial muscles. Numbness and tingling (paresthesias) are common symptoms.

Skin: A common symptom is cutis laxa as well as ptosis of the eyelids. In addition, other organs may be affected: heart (cardiac arrhythmias), kidneys, connective tissue (carpal tunnel syndrome).

The gold standard for diagnosis is genetic testing for one of the causative mutations. In case of positive family history and typical symptom complex (latticed corneal atrophy, peripheral facial nerve palsy, cutis laxa), a Gelsolin amyloidosis is very likely.

Unfortunately, a causal treatment is not yet available. In this respect, treatment must be symptom-oriented.

Life expectancy is not significantly reduced.

1. Bürmann J et al. (2011) Neurological manifestations of AGel amyloidosis (Meretoja's syndrome) in a German family. Fortschr Neurol Psychiatr 79: 238-241.
2. Kiuru-Enari S et al (2005) Cutis laxa in hereditary gelsolin amyloidosis. Br J Dermatol 152:250-257.
3. Koskelainen S et al (2020) Severe elastolysis in hereditary gelsolin (AGel) amyloidosis. Amyloid 27: 81-88.
4. Pihlamaa T et al. (2016) Increasing amount of amyloid are associated with the severity of clinical features in hereditary gelsolin (AGel) amyloidosis. Amyloid 23:225-233.