Researchers have reported the first case of familial amyloid polyneuropathy (FAP) with chronic dry cough — caused by a less common mutation — in a large Chinese family.
The case report, “Familial amyloid polyneuropathy with chronic paroxysmal dry cough in Mainland China: A Chinese family with a proven heterozygous missense mutation c.349G>T in the transthyretin gene,” was published in the Journal of Clinical Neuroscience.
FAP is a rare, progressive disorder caused by more than 130 different mutations in the TTR gene, which provides instructions to produce a protein called transthyretin.
TTR mutations lead to an unstable protein structure, and to the formation and accumulation of toxic amyloid aggregates mainly in the nerves, heart, kidneys, and eyes, ultimately causing tissue damage.
Increasing evidence has pointed out that FAP patients often show damage of the nerves that control involuntary body functions (autonomic neuropathy) before the impairment of peripheral nerves that control sensation and movement in the arms and legs (peripheral neuropathy).
Autonomic neuropathy can lead to postural hypotension — when blood pressure drops upon standing, leading to dizziness or fainting — heart abnormalities, gastrointestinal disorders, weight loss, and reduced sweating, while peripheral neuropathy can cause abnormal sensations in the legs and feet, such as numbness, tingling, or burning.
Researchers in China have now reported the first case of FAP with chronic dry cough, in a large Chinese family.
A 58-year-old man was admitted to the Xiangya Hospital – Central South University, in Changsha due to progressive bilateral muscular weakness and atrophy in the lower extremities for three years accompanied with mild numbness of the limbs.
He also had experienced hypotension for two decades, chronic dry cough — spontaneous or triggered by cool wind, smoke, and other intense odors — for four years, severely decreased appetite for several years, and alternating diarrhea and constipation in the previous year.
Clinical examination revealed symmetrical muscle weakness and atrophy in his legs, mild sensory involvement, and was unable to identify other respiratory disease or cause of the severe attacks of coughing.
The patient was the youngest of seven siblings, and his father and three elder brothers developed similar symptoms in their late 50s, which progressed to walking inability, leading to their death due to complications of staying in bed. They were misdiagnosed as having cervical spondylosis, lumbar spondylosis, or spinal muscular atrophy.
Among the three surviving siblings, one sister presented with progressive degeneration of the nerves, autonomic neuropathy and bilateral carpal tunnel syndrome — compression of the median nerve in the wrist that can cause tingling, numbness, and pain in the hand and fingers.
Genetic testing on the patient showed the presence of the known c.349G>T (p.Ala117Ser) mutation in TTR gene, which causes a switch in amino acids — the building blocks of proteins — in the TTR protein. Additional tests on the three surviving siblings revealed that only the symptomatic sister had the mutation.
While this less-common mutation was firstly and mainly described in Chinese families from Taiwan, this is the first report of the presence of this mutation in a family from Mainland China. The team speculated that this mutation may be relatively common in the Chinese population.
The team highlighted that the main clinical features of the reported family were slow progression, muscular weakness and atrophy of the legs due to neurodegeneration, significant autonomic neuropathy, mild sensory impairment, and chronic dry cough.
Recurrent and strong coughing attacks were never mentioned before in FAP patients, but increasing evidence has suggested an association between inherited polyneuropathy — the most common form of peripheral neuropathy — and chronic dry cough.
The researchers noted that additional studies are required to confirm this association and understand its cause, and that they will continue to follow the family to assess the whole disease course of this FAP associated with the c.349G>T mutation.
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