Rukavina Type Amyloid Polyneuropathy

At a glance

A very rare form of amyloid polyneuropathy. Cardiomyopathy has also been reported with this disorder.

Synonyms

Amyloid Polyneuropathy Indiana Type; Hereditary Neuropathic Amyloidosis II; Prealbumin-84 Amyloidosis Type II; Senile Systemic Amyloidosis Syndrome; Dysprealbuminemic Hyperthyroxinemia.

History

First described by J. G. Rukavina in 1956.

Genetic inheritance

Autosomal dominant.

Pathophysiology

Mutation in the transthyretin (prealbumin) protein located on 18q11.2-q12.1. This protein maintains normal levels of thyroid hormone, retinol, alpha-1-Antitrypsin, and retinol-binding protein in the circulation. Amyloidosis is a heterogeneous disease that results from the deposition of toxic insoluble beta-sheet fibrillar protein aggregates in different tissues. Two main types of amyloidosis affecting the heart are (1) light chain amyloidosis—a clonal plasma cell disorder due to the overproduction and misfolding of antibody light chain fragments and (2) transthyretin amyloidosis (ATTR). Transthyretin is a tetrameric serum protein that is synthesized primarily by the liver. Accumulation of TTR causes cell toxicity and tissue death. ATTR occurs in two types: nonmutated (senile/wild type) or mutated transthyretin with autosomal dominant inheritance (familial type).

Diagnosis

Demonstration of amyloid deposition in various tissues. The specific amyloidosis type is based on the genetic demonstration of a mutation in the prealbumin protein (substitution of serine for isoleucine at position 84). Onset is usually in the fifth decade of life. Neuropathic manifestations begin and predominate in the upper limbs. Carpal Tunnel Syndrome is a characteristic.

Clinical aspects

The disease is milder in females, appearing in adult age, and progressing slowly, with a 20-year survival time. Autonomic dysfunction is an early finding with orthostatic hypotension. Vitreous opacities and visceral manifestations (cardiac and renal amyloidosis) are milder than in amyloidosis I.

Precautions before anesthesia

Detailed medical history and physical examination for cardiac involvement of amyloidosis (diastolic cardiac dysfunction, cardiac failure) and conduction problems (clinical, ECG, Holter, echocardiography, radionuclide imaging if necessary) must be obtained. If the patient is carrying a permanent pacemaker, a preoperative pacemaker check is advised. Evaluate renal function (clinical, echocardiography, laboratory) and thyroid hormones and function (free thyroxin and thyroid-stimulating hormone levels). A thorough assessment for signs of severe autonomic dysfunction such as orthostatic hypotension must be obtained.

Anesthetic considerations

Be prepared for a high degree of cardiac conduction block. A transcutaneous pacing device must be available in the operating room. If the patient is equipped with a pacemaker, the usual precautions are applicable including preoperative pacemaker check. Watch for hemodynamic instability caused by autonomic dysfunction. Consider the existence and severity of the polyneuropathy and autonomic dysfunction before using regional anesthesia (lumbar epidural anesthesia described).

Pharmacological implications

Since alpha-1-antitrypsin ...