Two siblings who had been diagnosed with hereditary transthyretin amyloidosis (hATTR) early in life experienced disease progression with ocular and central nervous system involvement after several years of orthotopic liver transplant (OLT) and wellness.
The case report was described by Di Paolantonio and colleagues in Neurological Research.
Given the clear progression of symptomatology, the siblings initiated therapy with a gene silencer, patisiran (Onpattro®). At a 12-month follow-up evaluation, the siblings showed no evidence of neuropathy progression.
“Sharing similar OLT therapeutic effects, patients treated with gene-silencers could have a CNS and ocular hATTR progression,” explained Di Paolantonio and colleagues. “Despite the existence of these innovative drugs, hATTR treatment deserves an even more challenging approach for the next years: newer drugs able to stop TTR synthesis in central nervous system and to degrade the already existent deposits throughout the body are needed for the best management of our patients.”
Read more about hATTR therapies
Sibling 1 complained of impotence after previous good functioning, paresthesias at 4 limbs, and gastrointestinal symptoms at the age of 21 years, while sibling 2 suffered from paresthesias at 4 limbs and leg weakness at the age of 30 years. They were treated with OLT at 24 and 39 years old, respectively, after genetic confirmation of Val30Met hATTR.
Twenty-four (case 1) and 20 (case 2) years after OLT, the siblings experienced worsening of the previous neuropathy and developed new motor and sensitive symptoms.
Sibling 1 experienced a reappearance of paresthesias at the limbs and gastrointestinal symptoms, together with visual impairment, mild impairment of kidney function, shortness of breath, and transient ischemic attacks. Clinical evaluation revealed mild strength impairment at the extensor longus hallucis, absent tendon reflexes at the ankles, and sensory-motor axonal polyneuropathy. He scored 6 points on the Neuropathy Impairment Scale (NIS) and 37 points on the Norfolk Quality of Life (QOL) scale.
Ophthalmologic evaluation showed bilateral cataracts, a scalloped iris, vitreous depositions, and increased intraocular pressure.
Read more about hATTR diagnosis
Sibling 2 presented to the hospital with hypoesthesia with a “stocking-and-glove” pattern, a decline in extensor longus hallucis strength, and absent tendinous reflexes at 4 limbs. He scored 24 points on the NIS and 46 points on the Norfolk QOL.
In addition, he showed evidence of cardiovascular dysautonomia, axonal sensory-motor polyneuropathy, and several brain alterations. Ophthalmologic evaluation showed vitreous opacities, bilateral scalloped irises, optic nerve atrophy, and mild lens sclerosis.
Reference
Di Paolantonio A, Romano A, Guglielmino V, et al. Central nervous system involvement in two siblings affected by hereditary transthyretin amyloidosis 30 years after liver transplantation: a model for gene-silencing therapies. Neurol Res. Published online May 3, 2023. doi:10.1080/01616412.2023.2208470
