Researchers identified a very rare mutation in a Libyan man who was diagnosed with late-onset familial amyloid polyneuropathy (FAP), according to a case report.
The report, titled “Familial amyloid polyneuropathy due to p.ALA140 SER mutation,” appeared in the journal Neurology India.
FAP is a rare, progressive disorder caused by more than 100 different mutations in the TTR gene, which contains instructions to produce a protein called transthyretin. TTR gene mutations lead to an unstable protein structure and to the formation and accumulation of toxic amyloid aggregates in peripheral nerves and organs.
The build-up of toxic aggregates results in a variety of symptoms, which can complicate and delay a correct diagnosis.
Commonly, FAP patients show damage of the peripheral nerves that control sensation and movement in the arms and legs (peripheral neuropathy), and of the nerves that control involuntary body functions (autonomic neuropathy). Heart abnormalities are also often found in these patients.
Peripheral neuropathy can lead to abnormal sensations in the legs and feet, such as numbness, tingling, or burning, and autonomic neuropathy to postural hypotension — when blood pressure drops upon standing, leading to dizziness or fainting — gastrointestinal disorders, weight loss, and reduced sweating.
A confirmed diagnosis of FAP usually requires a tissue biopsy and genetic testing.
Researchers in Turkey reported the case of a 55-year-old Libyan man who was diagnosed with late-onset FAP, where they identified a very rare mutation of the TTR gene.
He reported progressive numbness, tingling, and weakness in both hands and feet, problems walking, a 66 pound weight loss, and gastrointestinal problems over the last three years. He had a history of walking difficulties and heart disease in his family.
A clinical examination confirmed symptoms of peripheral neuropathy with severe weakness in the limbs, loss of tendon reflexes, sensory symptoms, and severe carpal tunnel syndrome — characterized by pain, numbness, and tingling in the hands and arms.
An echocardiogram also suggested a form of cardiomyopathy, a disease of the heart muscle that impairs its capacity to pump blood to the rest of your body.
All these symptoms led to the suspicion of a late-onset FAP, which was confirmed by a tissue biopsy and genetic analysis. The genetic analysis revealed the presence of a very rare mutation, p.Ala140Ser, which had been reported in only two other cases. (The most common TTR gene mutation leading to FAP is Val30Met, researchers said.)
One study reported a woman who had FAP symptoms at age 62, with impaired motor and sensory functions (peripheral neuropathy), as well as cardiomyopathy. She was of Afro-Caribbean descent, which was similar to the ethnicity of the male patient reported in the present study.
Another study described the case of an Italian woman who was 64 when her symptoms began. She had severe carpal tunnel syndrome and other symptoms of impaired motor and sensory functions (peripheral neuropathy), as well as gastrointestinal symptoms and weight loss (autonomic neuropathy).
The researchers said FAP should be suspected in patients with progressive peripheral neuropathy, autonomic neuropathy, weight loss, and cardiac disorders of unknown cause.
“Genetic testing should be considered for the accurate diagnosis of this treatable life-threatening disease,” they concluded.
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