Heart damage-linked gene caused FAP-like symptoms: Case report
Man had neurological symptoms, no heart involvement
A man carrying p.Val142Ile, a TTR gene mutation often linked to a condition related to familial amyloid polyneuropathy (FAP) but causing heart damage instead of nerve damage, developed FAP-like neurological symptoms and no heart involvement, a case report showed.
“The particularly unusual [genetic profile-clinical profile] association distinguishes this case from the classic description of transthyretin amyloidosis secondary to p.Val142Ile,” the researchers wrote.
The case study, “Polyneuropathy as an initial manifestation of Hereditary [Transthyretin] Amyloidosis (ATTRV) in a young patient: Case report of a diagnostic challenge,” was published in Clinical Medicine Insights: Case Reports.
Hereditary transthyretin amyloidosis, or hATTR amyloidosis, refers to conditions marked by the accumulation of toxic clumps of abnormal transthyretin protein in the body’s tissues and organs due to mutations in the TTR gene.
Depending on the disease-causing mutation, hATTR amyloidosis can present either neurological or heart-related symptoms or a combination of both.
Muscle pain, weakness
In FAP, toxic transthyretin aggregates accumulate mostly in peripheral nerves — those located outside the brain and spinal cord — causing symptoms of nerve damage such as muscle weakness and abnormal sensations.
The Val30Met mutation, also known as Val50Met, is the most common cause of FAP, while the Val142Ile, or V142I, mutation is most commonly associated with heart involvement.
The team of researchers in Colombia reported the case of a 27-year-old man whose FAP-like disease was found to be caused by the V142I mutation.
The man arrived at the emergency department complaining of muscle pain, loss of sensation, and muscle weakness in the lower limbs. He also reported night sweats and involuntary weight loss, as well as difficulty swallowing and back pain. He had experienced the symptoms intermittently over the past two years.
Other institutions had considered possible diagnoses, and the man received treatment despite no confirmed diagnosis, which resulted in no symptom relief.
Physical examination found a decrease in muscle strength across all muscle groups, mainly in the lower limbs, as well as a loss of sensation in the extremities and pain upon palpation. Blood analysis revealed normal blood parameters and kidney function.
Electromyography and nerve conduction tests to assess the health of muscles and the nerves that control them came back normal. Creatine kinase levels, which can be a marker of tissue damage, were also normal.
Imaging scans showed signs of inflammation in the joints where the spine meets the pelvis, and swelling of fatty tissue in the lower spine. A video swallowing test confirmed alterations in swallowing and loss of muscle strength in oral and facial muscles.
Further testing excluded the possibility of an autoimmune disease, a psychiatric condition, and intoxication with heavy metals that was considered due to the patient’s occupation as a metal-mechanic worker.
During hospitalization, the man experienced fever and pain in the right part of the head, with several tests in that region showing muscle and blood vessel inflammation typically related to nerve damage. He had no other manifestations of blood vessel inflammation.
Symptoms suggest nerve-fiber damage
While “the imaging and laboratory studies did not show any evidence of neurological involvement,” the researchers wrote, some of the man’s symptoms suggested damage to small nerve fibers, which control sensations and involuntary bodily functions, including sweating.
After excluding other potential causes of his condition, the man was found to carry a V142I mutation in the TTR gene, confirming a diagnosis of hATTR amyloidosis.
Although this mutation is usually associated with heart involvement, it can occasionally cause damage to multiple nerves, or polyneuropathy, which explained all of the man’s clinical manifestations, including also gastrointestinal symptoms and urinary problems, the team noted.
Heart tests showed no evidence of heart involvement.
The man was started on Tegsedi (inotersen), an approved FAP treatment, to ease neurological symptoms and slow disease progression, and on medications to help manage pain.
Because of his functional decline and lack of familial support, the man was transferred to a chronic care facility with a therapeutic plan that included physical, speech, and occupational therapy. After two doses of Tegsedi, the pain and neurological symptoms had not eased, but they also did not worsen.
“The patient’s presentation was unusual, with predominantly polyneuropathic involvement,” the researchers wrote, adding that “the time to diagnosis was approximately 2 years from the onset of symptoms.”
“Challenges faced before achieving an early diagnosis included the high [variability] in symptomatology, the absence of a known family history, and the high number of [other] diagnoses that could explain the patient’s symptomatology,” the team wrote. An “orderly and focused diagnostic process, with high diagnostic suspicion, allowed us to rule out differential diagnoses and approach the definitive diagnosis based on the patient’s clinical history and physical examination,” they added.
The case, the researchers concluded, “highlights the significance of considering this diagnosis in patients with [problems in voluntary bodily functions] and polyneuropathy without an apparent cause.”
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