Familial amyloid neuropathy: Unusual etiology in clinical practice

Ashwani K Uttam¹, Kameshwar Prasad¹, Mehar C Sharma², Elanthenral Sigamani²,  
¹ Department of Neurology, All India Institute of Medical Science (AIIMS), New Delhi, India
² Department of Neuropathology, All India Institute of Medical Science (AIIMS), New Delhi, India

Correspondence Address:
Kameshwar Prasad
Department of Neurology, All India Institute of Medical Science (AIIMS), New Delhi
India

Full Text

Sir,

A-30-old man presented with weakness and numbness of left foot and leg of 3 years duration and similar complaints in right lower limb of 2΍ years duration. In addition, he also had progressive hoarseness of voice, diarrhea alternating with constipation, excessive sweating, erectile dysfunction, urgency, postural dizziness and significant weight loss despite good appetite of 2 years duration and developed proximal weakness of lower limbs since 1 year. He reported that his 20 years elder brother, who committed suicide at the age of 32 years, had clawing of hands. Examination revealed regular pulse rate of 78/min, supine blood pressure 100/68 mmHg with a drop to 74/50 mmHg on standing after 3 minutes, and heart rate variability with deep respiration was 10. There was marked generalized wasting, mild hypotonia, and weakness: Upper limbs proximal 4+/5, distal 4-/5 and lower limbs proximal 4-/5 and distal 1/5. There was graded sensory loss of 25% for pain and temperature below knees. Proprioception was impaired at great toe and vibration up to ankle. Deep tendon reflexes were diminished in upper limbs and absent in lower limbs. Plantar reflex was flexor on both sides. Peripheral nerves were not thickened. Nerve conduction study revealed sensorimotor axonal neuropathy [Table 1]. Detailed work-up for the other causes of neuropathy was negative. Ultrasound of abdomen revealed mild splenomegaly. Sural nerve biopsy showed amyloid deposition [Figure 1]a-c with marked axonal loss and demyelination. His abdominal fat pad biopsy was also positive for amyloid [Figure 1]d. 2D-Echo showed hypertrophic cardiomyopathy with diastolic dysfunction. Beta-2 micro globulin, serum IgG, IgA, IgD, bone marrow examination, and skeletal survey were all normal. Diagnosis of amyloid polyneuropathy, probably familial in view of claw hands in his brother was made.{Figure 1}{Table 1}

Familial amyloid polyneuropathy (FAP) and primary systemic amyloidosis (AL) can present with neuropathy, and neuropathy has almost never been found in secondary amyloidosis. [1] FAP is of three forms; transthyretin FAP (TTR-FAP), apolipoprotein A-1 FAP, and gelsolin FAP. Transthyretin FAP is the most common type. Two patterns of sensorimotor deficit occur in the TTR-FAP form. The most common deficit is sensorimotor polyneuropathy; the other has focal deficits resulting from local deposition of amyloid. [2] Some patients deteriorate rapidly because of autonomic dysfunction and rapid progression of the sensorimotor deficit. [2] Significant autonomic dysfunction in this patient was a clue to the clinical diagnosis. Hoarseness of voice could be attributed to amyloid deposition in vocal cords as we could not find any neurological cause. Our patient did not seem to have apolipoprotein A1 and gelsolin FAP as both the forms present with extra neurological involvement but not peripheral neuropathy. We presume that his elder brother who had clawing of hands probably had amyloid neuropathy. We finally diagnosed our patient as transthyretin FAP but could not confirm it due to unavailability of mutation analysis and immunohistochemistry. Only two cases of FAP and one case of primary AL amylodosis-associated neuropathy have been reported from India [3],[4],[5] and in both FAP cases, fat pad biopsy was not done. Positive fat pad biopsy for amyloid emphasizes that systemic involvement does not negate possibility of FAP.

References