Rare Case: Upper Limb Symptoms Preceded FAP Val30Met Mutation Diagnosis

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by Alice Melao |

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late-onset FAP

Researchers reported a rare case of familial amyloid polyneuropathy (FAP) in a patient with TRR gene Val30Met mutation who was experiencing impaired upper limb sensation and numbness.

The case was described in “A Val30Met sporadic familial amyloid polyneuropathy case with atypical presentation: upper limb onset of symptoms,” which was published in the journal Acta Neurologica Belgica.

FAP, or transthyretin (TTR) amyloid polyneuropathy, is a rare disease caused by genetic mutations in the TTR gene. More than 100 different genetic variants have been linked to this disease. Affecting up to 50 percent of FAP patients worldwide, the most common mutation results from an amino acid substitution in the position 30 in the gene sequence, identified as Val30Met.

In Portugal, Sweden, and Japan, where it is endemic (found most frequently), the Val30Met mutation is the predominant genetic cause of the disease. In the rest of the world, the genetic features of the disease are more variable, as are its clinical symptoms.

A research team at Istanbul University presented the case of a 66-year-old male FAP patient with the Val30 mutation and a rare disease course.

For three years he had experienced progressive numbness and pain in his right hand. His condition  progressively declined and the symptoms spread to the left hand. Based on these initial symptoms he was diagnosed with carpal tunnel syndrome affecting both hands, for which he underwent surgery.

Despite the treatment, his symptoms continued to progress with tingling and numbness spreading to his forearms, followed by weakness in both hands. At this point no significant symptoms affecting his lower limbs were reported.

Only two years after the onset of the upper limb symptoms he started to have numbness in the sole of his feet, which was followed by pain and weakness in both legs.

For three years he had recurrent constipation, an upright posture, and was impotent, all symptoms suggestive that his autonomic nervous system was impaired.

Based on these findings, he was diagnosed with chronic inflammatory demyelinating polyneuropathy, and initiated treatment with prednisolone for six months.

A new physical examination showed that he had excessive constriction of the pupils of both eyes, peripheral muscle weakness, and reduced sensation in the upper and lower limbs.

Nerve conduction studies revealed he had signs of nerve cell damage and loss of the cell’s protective myelin layer affecting the motor and sensory cells. Because his family had history of cardiac diseases, an evaluation of the heart was performed, which revealed some structural changes associated with amyloid deposition. Also analysis of salivary gland tissue confirmed the presence of amyloid infiltrates in blood vessels’ walls.

Genetic testing provided the final evidence that he had amyloid-associated neuropathy; he had the Val30Met TTR gene mutation. After the final diagnosis he started treatment with 20 mg per day of Vyndaqel (tafamidis).

“Upper limb onset axonal polyneuropathy is a rare presentation in general practice and was not reported in TTR-FAP patients in non-endemic regions,” the researchers wrote. “Careful examination and clinical suspicion is mandatory for reducing the misdiagnosis of the atypical cases,” they suggested.