The case of a woman of Afro-Caribbean descent with early onset transthyretin (TTR) amyloidosis, who was found to carry a TTR mutation more commonly seen in those of Celtic descent, showed that this disorder can be more varied than previously known.
Titled “Early-Onset of Transthyretin Amyloidosis in a Young Afro-Caribbean Woman With Thr60Ala Mutation,” the report was published in JACC: Case Reports.
Hereditary ATTR amyloidosis, caused by mutations in the TTR gene, has a spectrum of clinical manifestations, or ways the disease affects patients.
When patients experience symptoms of polyneuropathy, or nerve damage resulting in numbness, tingling, and pain, they have a subtype of the disease called familial amyloid polyneuropathy (FAP). But some patients may experience cardiac symptoms only, or a combination of heart-related and polyneuropathy symptoms.
Researchers now reported the case of a 23-year-old woman, born in St. Lucia, who was treated at Columbia University Medical Center, in New York, for a complex pattern of symptoms affecting multiple body systems.
The woman reported daily abdominal pain, rated six out of 10, with 10 as most severe, that grew worse with meals. Other symptoms included loss of appetite leading to weight loss, nausea, vomiting, and constipation.
The patient also experienced cardiovascular symptoms such as dizziness, chest pain, and the feeling of her heart skipping beats upon exertion. Further additional complaints included fatigue, exhaustion, difficulty breathing, and swelling in the legs.
Two years before, she had been treated for gastritis but reported that her abdominal pain returned the year following that treatment. Beyond that pain, she started vomiting up bile, lost 30 lbs. over a few months, and developed numbness and tingling in her hands and feet, as well as dizziness.
At that time, she had difficulty performing daily chores due to fatigue, difficulty breathing both upon exertion and when laying down, and experienced swelling in her legs.
Upon her hospital admission, the woman appeared thin and emaciated, according to the case report, but her vitals were largely normal, except for a slight cardiac irregularity. She also displayed some weakness in her lower legs, had no ankle reflexes, and experienced some distal sensory loss, which is the loss of sensation in the arms, legs, hands and feet.
Lab tests were normal and a computed tomography scan of her abdomen found no evidence of bowel obstruction. An echocardiogram (ECG) revealed an elevated heart rhythm.
Nerve conduction tests, which measure the speed of transmission along the nerves, showed signs consistent with axonal sensorimotor polyneuropathy, in which nerve damage occurs throughout the body.
Tests for abnormalities of the autonomic — involuntary — nervous system revealed multiple heart problems.
An abdominal fat pad biopsy, which is an examination of a fat tissue sample from the abdomen, revealed amyloidosis. Physicians confirmed TTR by biochemical testing, leading to a diagnosis of TTR amyloidosis, featuring disease of both the nerves and heart.
Genetic testing showed that the patient carried the Thr60Ala mutation, more often seen in TTR amyloidosis among people of Scottish and Irish descent.
Finally, a pedigree analysis found 13 other family members over three generations affected by similar symptoms, several of whom had died at an early age.
Over four years of follow-up visits, the woman’s gastrointestinal and cardiovascular symptoms have diminished, according to the physicians, and neurological exams have shown no signs of disease progression. The researchers evaluating her case reported that she now has more functional capacity than when she was first diagnosed.
The patient’s case was unusual, both for the mutation she carried and for the early onset of her condition. TTR amyloidosis patients of West African descent more often carry the Val122Ile mutation, and both that and the Thr60Ala mutation more typically associate with amyloidosis in a patient’s sixth or seventh decade, during the individuals 50s or 60s.
The early onset of this patient’s condition and its hereditary pattern suggested that this case may still have an undefined genetic or environmental cause.
The investigators concluded that this patient’s mixed cardiac and neurological symptoms, as well as her uncommon mutation and early onset of the disorder, call for further studies of the relationships between biochemical measures of TTR and clinical features.
These, they say, may shed light on “the biological underpinnings of this devastating disease and be useful in identifying the mechanism of early disease.”
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