Rare Case of FAP and Mitochondrial Disease Reported in Study

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by Alice Melao |

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The rare case of a patient in Italy who had familial amyloid poyneuropathy (FAP) in addition to mitochondrial disease was described in a report published in the journal Amyloid.

The report was titled “Progressive axonal polyneuropathy in a mitochondrial disorder: an uncommon association with familial amyloid neuropathy.”

The patient, a 67 years-old man, was first referred to the neurology team due to a four-year history of numbness and tingling affecting the lower limbs with associated walking difficulties and exercise intolerance.

After a comprehensive clinical evaluation and muscle tissue biopsy analysis, he was found to have abnormal expansion and damage of mitochondria — the energy-producing area of cells — and impaired mitochondria activity. Also, his muscle fibers were found to have abnormal structures with accumulation of fatty compounds.

Based on the findings he was discharged with a diagnosis of mitochondrial disease that was affecting a number of systems.

His condition remained stable for about two years, but then the patient got considerably worse.

A new neurological evaluation revealed that his walking capacity was significantly reduced. The patient was only able to walk for a few meters with bilateral support. He had also developed loss of sensation in hands and feet.

He showed severe weakness of distal muscles of the lower limbs (feet and lower legs), whereas proximal muscles (closer to the body) of the upper and lower limbs were only mildly affected. He was also found to have reduced tendon reflexes in the upper limbs and absent in lower limbs.

Further evaluations confirmed he had worsening peripheral nerve cell damage (polyneuropathy) that could explain several of these symptoms.

Based on these manifestations the clinical team suspected that he had developed an inflammatory process in response to its mitochondrial disease condition. But additional evaluations failed to confirm this hypothesis and a target treatment to prevent immune reactivity failed to ease his symptoms.

Supported by the nerve cell conductance results, additional examinations were performed to explore the presence of FAP, or transthyretin (TTR) amyloid neuropathy.

The analysis confirmed the accumulation of TTR aggregates in the abdominal fat, but no heart condition due to TTR accumulation was detected. A genetic test detected a mutation in the TTR gene that was consistent with a diagnosis of FAP.

“Occurrence of two rare genetic diseases is a rare condition but [has been previously] reported in neurology,” the researchers stated.

In many cases, “TTR-related amyloidosis is often misdiagnosed in favor of other more common or treatable conditions,” they wrote. But in this case, the rapidly progressing peripheral nerve cell damage “was atypical for the [mitochondrial disease] setting and prompted us to search for additional causes,” they said.

Collectively, the team believes that this report highlights that in the presence of progressive neuropathy, patients “should always be screened for amyloid, also in patients with other rare or multisystemic diseases.”