Autonomic failure in primary amyloidosis.
ABSTRACT Amyloidosis is an uncommon plasma cell dyscrasia affecting Multisystem, characterized by deposition of amyloid proteins in extracellular spaces and the tissues. Reported incidence of amyloidosis is 8 cases per million per year. Deposition of amyloid fibrils occurs in peripheral nerves in 20% of the cases in Primary Amyloidosis. Though. polyneuropathy is one of the presenting manifestations in cases of Primary Amyloidosis, pure autonomic failure without involving peripheral nerves is not a documented entity. Here, we present a case of Primary Amyloidosis presenting as Pure Autonomic Failure (Dysautonomia).
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ABSTRACT: BACKGROUND: Renal amyloidosis is an unusual diagnosis in patients undergoing kidney biopsy. Knowledge of the clinical features and long-term outcomes is still very limited. The current study represents our single-center experience in the past 27 years. METHODS: Six thousands renal biopsies were performed between January 1983 and June 2010 at Taichung Veterans General Hospital. Of them, 720 cases were from renal allograft and 5280 were from native kidneys. A retrospective study via chart review was conducted to identify cases of renal amyloidosis. The clinical features as well as laboratory data at presentation and subsequent follow-up were retrieved and analyzed. RESULTS: Among 5280 cases of native kidney biopsies, 35 renal amyloidosis (0.66%) were identified. The mean follow-up duration is 1155 days. The incidence of renal amyloidosis among proteinuric patients appeared to be increasing. The male to female ratio was 24:11. Seventeen (48.6%) cases were of light chain amyloidosis (AL) type while the others were of non-AL types. The mean age was 61.7 ± 12.9 years, while the duration between apparent onset and kidney biopsy was 299.4 ± 312.2 days. Most of the cases (83.9%) had nephrotic-range proteinuria. The mean 24-hour urine protein was 7.4 ± 4.7 g (median: 6.48 g/day, 2.13-22.9 g/day), serum albumin, 2.39 ± 0.7 g/dL; total cholesterol, 327.5 ± 144 mg/dL; and triglyceride, 223.7 ± 150 mg/dL. Hematuria occurred in 40% of the cases. The eGFR at renal biopsy was 56.3 ± 28.2 mL/min. There was no obvious enlargement in renal size (right kidney: 102.7 ± 15.6 mm, left kidney: 107.9 ± 14.2 mm). The one-year and five-year patient survival was 42.9% and 17.9%, respectively. Logistic regression analysis revealed that eGFR was the only predictive factor for patient survival. CONCLUSION: Elderly patients with nephrotic syndrome should prompt the suspicion of renal amyloidosis, especially in those with nephritic syndrome and relatively low blood pressure. Given the increasing incidence and poor prognosis, early diagnosis and a search of the underlying etiology of amyloidosis are mandatory. (Acta Nephrologica 2011; 25: 113-118)Acta Nephrologica. 01/2011; 25(3):113-118.
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ABSTRACT: Familial amyloidosis with polyneuropathy (FAP) sometimes courses with vitreous amyloid. The aim of this study was to evaluate the incidence of glaucoma after vitrectomy in FAP patients. A total of 79 eyes of 42 liver transplanted FAP patients and 16 eyes of 16 non-FAP patients with rhegmatogenous retina detachment were collected. The patients were divided in to three groups: Group I - FAP patients with vitreous opacities submitted to vitrectomy, Group II - FAP patients without vitreous opacities and not submitted to vitrectomy and, Group III - non-FAP patients with rhegmatogenous retinal detachment submitted to vitrectomy. The Group I was subdivided into: Ia - "complete" vitrectomy; Ib - "incomplete" vitrectomy. The onset of glaucoma was considered when the intraocular pressure level was higher than 21 mmHg, with concomitant visual field abnormalities and optic nerve cupping. Post vitrectomy glaucoma was more frequent in Group I (56.1%) than in Group III (12.5%) and in Group II (10.5%). We observed a higher incidence of glaucoma in the Ia than in the Ib subgroup (86.4 vs. 21.1%) and earlier appearance in subgroup Ia (7.9 ± 3.6 vs. 39.5 ± 6.6 months). Vitrectomy induced the development of glaucoma in FAP patients.Amyloid: the international journal of experimental and clinical investigation: the official journal of the International Society of Amyloidosis 08/2012; 19(3):146-51. · 2.51 Impact Factor
- Amyloid. 06/2014;
© JAPI • VOL. 56 • DECEMBER 2008 www.japi.org 995
proteins.1-3 Six types of amyloidosis have been described
in literature – primary, secondary, haemodialysis-related,
hereditary, senile and localized. Primary amyloidosis (AL)
is associated with monoclonal light chains in serum/urine
with 15% of patients having multiple myeloma. Secondary
amyloidosis (AA) is associated with inflammatory, infectious,
and neoplastic causes3. As the symptoms like fatigue,
shortness of breath, edema, parasthesias and weight loss,
remain vague most of the times, the diagnosis is difficult
to reach. However, patients may present as nephrotic
range proteinuria with or without renal insufficiency,
cardiomyopathy, hepatomegaly, symptomatic peripheral
neuropathy, and autonomic failure.1,2 Autonomic failure
is always a part of symmetric peripheral neuropathy in
reported cases of primary amyloidosis. Here, we report a
case of Pure Autonomic Failure without involving peripheral
nerves in case of Primary Amyloidosis.
Mr. ABS, 50 years old previously healthy male presented
with history of giddiness for 1 and ½ years, especially while
getting up from lying down position and when beginning
to start walking. It was associated with feeling of blackout
sensation which used to get relieved on sitting down. The
giddiness progressively increased from initial 2-4 episodes
per week to present 2-4 episodes per day. There is no history
of increase in giddiness on movement of neck. There is no
history of rotation of surroundings, diplopia, tinnitus or
myloidosis is a rare multisystem disorder,
characterized by extracellular deposition of abnormal
There is no history of headache, weakness in limbs,
dysarthria, dysphagia, change of speech, paraesthesias
or dysaethesias, imbalance of gait, falls, tendency to fall
backwards, tremors or seizures. There is no history of
chest pain or palpitations. There is no history of bladder
involvement, hyper- or hypohydrosis. No history of drug
intake or toxins could be elicited. No history suggestive of
abnormal pigmentation was noted. Patient denied history
of Diabetes Mellitus and alcoholism.
Patient gave history of impotency for the same duration
– inability to get erection and ejaculation, no early morning
tumulescence and loss of libido associated with increased
frequency of stools.
There are no family members suffering from similar
Examination revealed severe orthostatic hypotension (BP
supine – 100/70 mm Hg and BP standing – 62/50 mm Hg).
His general and systemic examination was unremarkable.
Central nervous system (CNS) examination didn’t reveal
any involvement of pupils, cerebellar system or peripheral
nerves. All sensations were intact without any thickening
of peripheral nerves. ENT examination was normal. Patient
was evaluated in detail for cardiac autonomic neuropathy
as follows :
1. Postural hypotension – BP supine – 100/70 mm Hg and
BP standing 62/50 mm Hg (abnormal)
2. Sustained hand grip response – DBP 60 mm Hg initially
and DBP 64 mm Hg at the end of the test (abnormal)
3. Valsalva manoeuvre : RR/rr ratio – 1.0 (abnormal)
4. Heart rate response to standing : 30/15 RR ratio – 1.065
5. Heart rate response to deep breathing – RR max – RR
*Resident, Internal Medicine **Senior Nephrologist ***HOD Medicine
and Cardiology, Bharat Ratna Dr. Babasaheb Ambedkar Memorial
Hospital, Central Railway, Byculla, Mumbai - 400 027.
Received : 19.6.2008; Revised : 11.7.2008; Accepted : 2.9.2008
Autonomic Failure in Primary Amyloidosis
Aditi Pandit*, Savita Gangurde**, SB Gupta***
Amyloidosis is an uncommon plasma cell dyscrasia affecting Multisystem, characterized by deposition of amyloid
proteins in extracellular spaces and the tissues. Reported incidence of amyloidosis is 8 cases per million per year.
Deposition of amyloid fibrils occurs in peripheral nerves in 20% of the cases in Primary Amyloidosis. Though.
polyneuropathy is one of the presenting manifestations in cases of Primary Amyloidosis, pure autonomic failure
without involving peripheral nerves is not a documented entity. Here, we present a case of Primary Amyloidosis
presenting as Pure Autonomic Failure (Dysautonomia). ©
996 www.japi.org © JAPI • VOL. 56 • DECEMBER 2008
min – 1.0 (abnormal)
He underwent Head Tilt Test – positive with reproduction
of symptoms – heart rate accelerated to 102 bpm and BP
dropped to 60mm Hg systolic.
His hematological and biochemical reports were normal
except severe dyslipidaemia (Total Cholesterol – 341 mg%,
Triglycerides – 247 mg%, LDL Cholesterol – 262.3 mg%
and HDL Cholesterol – 29.3 mg%). His urine examination
revealed 3+ proteinuria with normal microscopy and 24
hours urinary proteins were 5.0 Gms. His ECG, 2-D Echo,
and Holter monitoring were normal. His MR Brain and
4-vessel MR Angio were normal. His NCV/EMG studies
were normal. His serum cortisol, aldosterone and thyroid
hormones were normal. USG Kidneys were normal. Serum
immunoelectrophoresis report revealed light chain
gammopathy (IgA lambda isotype).
Patient was subjected for renal biopsy which revealed
mesangial deposits, positive for Congo Red stain with
green fluorescence on UV light, confirming the diagnosis
of Primary Amyloidosis (Light Chain – AL).
A wide variety of medical conditions can present as
autonomic disorders – Primary conditions like Shy-Drager
syndrome, the Riley-Day syndrome, the Bradbury-Eggleston
syndrome or Secondary due to Diabetes, Alcoholism,
Nutritional deficiency, Toxins, drugs, paraneoplastic,
amyloidosis and others.4,5 Light-chain (AL) amyloidosis
is the most common form of systemic amyloidosis.6
Peripheral neuropathy and autonomic neuropathy is one
of the presenting manifestations of Primary Amyloidosis.4,5
Autonomic neuropathies are inherited or acquired (as
in amyloidosis) in which the autonomic nerve fibers are
selectively or disproportionately affected.7 Several familial
cases of amyloidotic polyneuropathy (FAP) have been
reported in literature.8,9 A case has also been reported
with primary amyloidosis with progressive hypotension.10
However, intensive search has not revealed a single case
of Autonomic Failure without involvement of peripheral
nerves due to primary amyloidosis. Our case emphasizes
the need of good clinical history and examination with
full investigational work up which revealed autonomic
neuropathy as the cause of orthostatic hypotension.
His neurological work up ruled other causes of primary
autonomic failure and his renal profile confirmed the
diagnosis of Primary Amyloidosis and the likely cause of his
pure autonomic failure. Chemotherapy with Thalidomide is
contemplated in the case.
Primary amyloidosis is a rare disease. Though peripheral
neuropathy with autonomic neuropathy is common
manifestation of primary amyloidosis, pure autonomic
failure in a case of primary amyloidosis is an unreported
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Res Clin Haematol 2005;18:709-27.
Gertz MA, Lacy MQ, Dispezieri A, Hayman SR. Amyloidosis : diagnosis
and management. Clin Lymphoma Myeloma 2005;6:208-19.
Ebert EC, Nagar M. Gastrointestinal manifestations of amyloidosis.
Am J Gastroenterol 2008;103:776-87.
Hollister AS. Orthostatic hypotension – Causes, Evaluation and
Management. West J Med 1992;157:652-57.
Wichser J, Vijayan N, Dreyfus PM. Dysautonomia – Its
Significance in Neurological Disease. Calif Med 1972;117:
Sanchorawala V. Light-chain (AL) amyloidosis : diagnosis and
treatment. Clin J Am Soc Nephrol 2006;1:1331-41.
Low PA, Vernino S, Suarez G. Autonomic dysfunction in peripheral
nerve disease. Muscle Nerve 2003;27:646-61.
Drugge U, Andersson R, Chizari F, Danielsson M, et al. Familial
amyloidotic polyneuropathy in Sweden : A pedigree analysis. J Med
Zalin A, Darby A, Vaughan S, Raftery EB. Primary
Neuropathic Amyloidosis in Three brothers. BMJ 1974;1:
10. Campbell TN, Goldman R. Primary amyloidosis with death due to
progressive hypotension. Calif Med 1966;104:208-11.