FAP Diagnosis Worth Considering in Patients with Neuropathy and Cardiac and Eye Issues, Case Report Shows

Jose Marques Lopes PhD avatar

by Jose Marques Lopes PhD |

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A woman diagnosed with late-onset familial amyloid polyneuropathy (FAP) showed severe sensory and motor neuropathy, or nerve damage, as well as eye and cardiac impairments, a case report describes.

The report, “Late-onset Transthyretin (TTR)-familial Amyloid Polyneuropathy (FAP) with a Long Disease Duration from Non-endemic Areas in Japan,” was published in the journal Internal Medicine.

Although several families with autosomal dominant FAP with an accumulation of a mutant version of transthyretin (TTR) have been reported in Japan, sporadic cases with unclear family history have also been found, including in non-endemic areas, meaning regions where there is less prevalence. In autosomal dominant disorders, the mutated gene is a dominant gene located in a nonsex chromosome.

Scientists from University of Tsukuba Hospital and Shinshu University School of Medicine in Japan described the case of an 84-year-old woman, who first visited their hospital in a wheelchair. She had complaints of muscle weakness and sensory disturbances in the extremities, and a history of hypertension and bradyarrhythmia, or slow heart rate.

She had started experiencing orthostatic dizziness — associated with low blood pressure when standing up — in her 50s. At the age of 78, she noticed impaired visual acuity in the left eye, followed by vitreous opacity, or floaters, frequently found in Japanese patients with FAP, and bilateral cataracts on examination.

Then, at 81 years old, she began experiencing tingling sensations in her fingers and toes, followed by shortness of breath and dizziness one year later. She also lost her appetite due to nausea.

On admission, the woman was underweight, with a body mass index of 15.4 kg/m3, her blood pressure was 100/52 mmHg, and she often had an irregular pulse rate. A neurological examination showed she had hearing loss in the right ear.

She exhibited muscle weakness predominantly in the distal extremities, and muscle atrophy, or shrinkage, in the bilateral interosseous dorsalis muscles (back of the hands), balls of the thumbs, hypothenar areas (also in the hand), and tibialis anterior, which is a large muscle in the leg. Her deep tendon reflexes, which refer to nerve reflexes that determine muscle contraction upon tapping, were absent in all limbs.

The patient also had a loss of sensation in all distal portions of the extremities, less vibration and position sensation in all limbs, dysesthesia (unpleasant and possibly painful sensations ), hypohidrosis (less sweat than usual), and nocturia (having to wake up during the night to urinate), as well as recurrent diarrhea and constipation.

Her N-terminal pro-brain natriuretic peptide — an indicator of heart failure — exceeded the normal reference values, while immunoglobulin A and M were below the lower limit. An analysis of the cerebrospinal fluid — the liquid surrounding the brain and spinal cord — revealed higher-than-normal protein concentration.

Abnormal cardiac function results were found on an electrocardiogram. And a type of exam called an ultrasonography showed an ejection fraction of 65% — meaning that 65% of the total amount of blood in the left ventricle is pushed out with each heartbeat — as well as other findings suggestive of left ventricular hypertrophy, or enlargement, and diastolic dysfunction. Marked orthostatic hypotension was found on the Schellong test.

Magnetic resonance imaging revealed only chronic ischemic changes in the head, while the patient’s spinal cord showed mild stenosis, or narrowing. Motor nerve conduction was abnormal in the median (extending from the arm to the hand), tibial (leg), ulnar (arm) and sural (leg) nerves. Further findings suggested peripheral neuropathy.

The researchers suspected that amyloid polyneuropathy was the cause of the patient’s severe peripheral neuropathy. A subsequent test revealed infiltration of lymphocytes, plasma cells, and eosinophils — a type of white blood cell — as well as amyloid deposits. A sural nerve biopsy showed a mild decrease in the number of nerves surrounded by a protective layer called myelin, but no significant inflammation.

Mutant TTR was then found. The additional presence of normal TTR led to a diagnosis of FAP with a Val30Met mutation, which is the most frequent in FAP patients with polyneuropathy.

Upon diagnosis, the woman started taking Vyndakel (tafamidis), which led to a partial improvement in her hand function. One year later, no remarkable changes were found in a nerve conduction study in the upper limbs.

Given the potentially long time it can take to diagnose FAP cases in non-endemic areas, the team recommends that “if patients have any autonomic dysfunctions and/or defects in the eyes or heart in addition to sensory and motor neuropathy, FAP should be considered as a differential diagnosis.”