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Year : 2015  |  Volume : 8  |  Issue : 6  |  Page : 822-825  

Fabry's disease

Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, Dilshad Garden, New Delhi, India

Date of Web Publication19-Nov-2015

Correspondence Address:
Laxmikant Ramkumarsingh Tomar
Department of Medicine, University College of Medical Sciences and Guru Teg Bahadur Hospital, University of Delhi, Dilshad Garden, New Delhi - 110 095
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/0975-2870.169938

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Fabry's disease is an X-linked multisystem disorder due to the deficiency of lysosomal enzyme α-galactosidase A, leads to accumulation of sphingolipids throughout the body. Key causes for premature death include cardiac and renal. Here, we present important clinical findings of such rare case.

Keywords: Cardiac, cutaneous, Fabry, renal

How to cite this article:
Tomar LR, Sonambekar AA, Gupta S, Gupta N. Fabry's disease. Med J DY Patil Univ 2015;8:822-5

How to cite this URL:
Tomar LR, Sonambekar AA, Gupta S, Gupta N. Fabry's disease. Med J DY Patil Univ [serial online] 2015 [cited 2020 Nov 28];8:822-5. Available from:

  Introduction Top

Fabry's disease was named after dermatologist Johannes Fabry. It is also named by different names such as Anderson-Fabry disease, angiokeratoma corporis diffusum and alpha-galactosidase A deficiency. It is multisystem disorder caused due to deficiency of α-galactosidase A leads to accumulation of spingolipids in different parts of the body. [1] Males are affected commonly. Females are generally asymptomatic, but severity of disease in female heterozygous may be as severe as in males.

Here we are highlighting some important clinical features of Fabry's diseases in our patient, like:

  1. Cutaneous manifestations,
  2. Autonomic dysfunction,
  3. Cardiac manifestations,
  4. Oral mucosal lesions,
  5. Raynaud's phenomenon, with some supportive laboratory investigations like derange renal functions and skin biopsy.

  Case Report Top

A 32-year-old male who presented to medicine outpatient department with complaints of absent sweating even during summer since childhood associated with a cutaneous eruption and oral mucosa redness at age of 10. There was also the history of Raynaud's phenomenon and burning pain in bilateral lower limbs for last 4-5 years. He also gave a history of pins like sensation, tingling and stiffness of hands and feet for last 4 years. His mother's brother also had history of absent sweating and he died at age of 38 years due to coronary heart disease. His sibling's and his son are phenotypically normal. On general examination blood pressure was 134/82 mm Hg, regular pulse rate of 78/min. There were small raised, purplish, nonblanching lesions present over the abdomen and back [Figure 1]. Oral cavity examination reveals non-hemorrhagic, reddish pinpoint mucosal lesion present over the soft palate [Figure 2]. Rest of system was normal on examination.
Figure 1: Angiokeratoma on abdomen and back

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Figure 2: Oral mucosal lesion on soft palate

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Investigations revealed Hb 11.6 g/dL, total leucocyte count of 8000/mm 3 , blood urea was 84 mg/dL, serum creatinine of 2.9 mg/dL, Na + 138 mEq/L, K + 4.0 mEq/L, total protein 6.9 g/dL, albumin 3.6 g/dL, serum calcium 8.3 mg/dL, serum uric acid 4.84 mg/dL. Urine examination showed 2+ proteinuria. Electrocardiogram (ECG) features suggestively of left ventricular hypertrophy. Echocardiography (ECHO) revealed concentric left ventricular hypertrophy with ejection fraction of 52%. Pulmonary function test (PFT) was normal. Cornea and fundus examination was normal. Abdominal ultrasonography revealed bilateral normal size kidney with increase in echogenicity and altered corticomedullary differentiation. Ear, Nose and Throat (ENT) examination was normal. Nerve conduction velocity study was normal. Skin biopsy shows numerous, dilated, thin-walled, endothelial cells that contain lipid-laden cytoplasmic vacuoles in the dermis, with a hyperkeratotic epidermis, features suggestive of Angiokeratoma Corporis Diffusum.

  Discussion Top

Dermatological manifestations may be the earliest sign that include angiokeratomas presents between age group 5 and 13. [2] This are characterized by slightly raised, purplish-red, non-blanching lesions due to weakening of the capillary wall within the epidermis and dermis. Other cutaneous manifestation includes anhydrosis or hypohydrosis. Different anatomic sites such as hips, back, thighs, buttocks, penis, scrotum and the oral mucosa and conjunctiva may involve. [3] Close differentials are angiokeratoma of scrotum. Diagnosis is mainly done by biopsy. Treatment of angiokeratoma includes a laser method that has shown mixed or discouraging results as this treatment did not prevent the formation of new lesions. [4] Topical moisturizers can be helpful to prevent fissures in the skin and secondary infections.

Cardiac involvement may be the key cause of premature death, because as disease advances left ventricular enlargement along with a reduction of ejection fraction occurs. 3-12% of patients with unexplained left ventricular hypertrophy have Fabry disease. [5] The earliest cardiac abnormalities include short PR interval, bradycardia, mild valvular insufficiency, arrhythmias, diastolic dysfunction. [6],[7] Raynaud's phenomenon, vasospastic angina or myocardial infarction can occur. Biopsy from cardiac lesions, usually, demonstrates sarcoplasmic vacuolization under light microscopy and cytoplasmic lamellated zebra bodies under electron microscopy. Therefore, these patients should be monitored by routine ECG and ECHO or Holter (24-h) monitoring to detect rhythm abnormalities. It should be done as a baseline and every other year if age ≤35 years every year thereafter. Sometimes magnetic resonance imaging may help to determine the amount of myocardium scarring. Coronary angiography should be done when clinical signs of angina are present. Treatment remains mainly symptomatic; if any vascular event occurs then patient should be treated with angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB), calcium-channel blockers and antiplatelet drugs. Cardiac pacing done when there are higher degrees of A-V blocks. When conservative management fails percutaneous transluminal septal myocardial ablation can be used.

Patients with renal involvement initially manifest as impaired filtration rate, proteinuria or impair tubular functions, later on progressed to chronic kidney disease (CKD). [8] Therefore, kidney function test along with 24 h urine or spot urine should be carried out in every Fabry patient. It should be done every 3 months in CKD stage 1 or 2 and >1 g/day of proteinuria or CKD stage 4, every 6 months if CKD stage 3 and every 12 months CKD stage 1or 2 and <1 g/day of proteinuria. Renal biopsies for baseline evaluation in patients presented with atypical sign and symptoms or if patient did not improve with treatment. Treatment should mainly focus on the control of blood pressure, lipids and proteinuria. ACE inhibitors and ARB are important therapeutic options. Renal transplantation is undertaken when patient reached end-stage renal disease.

Neurological dysfunction includes peripheral nervous system manifests as acroparesthesias, hypo-or anhidrosis and stroke. These neurological manifestations are thought to be due to ischemic injury of nerve fibres due to prothrombotic state and metabolic failure, that causes disruption of mainly small-fiber involvement (both myelinated and unmyelienated) along with dirupition of dorsal root and autonomic ganglia. Onset of neurological symptoms occurs earlier in males than in females. [9] Episodic pain crises that last from a few minutes to several weeks and can be associated with fatigue, low-grade fever and joint pains aggravated by stress of physical activity. Treatment is symptomatic that includes Phenytoin, carbamazepine, gabapentin or topiramate are used for treatment of painful crises, avoid factors that precipitate pain and maintain hydration. Antiplatelet drugs can be used as prophylaxis or treatment of stroke.

Ocular findings show pale, spiral streaks in the corneal epithelium known "cornea verticillata." Corneal manifestations present in over 90% of the patients and may be useful for early recognition of disease. [10] These patients are also susceptible to the develop cataracts and blood vessels of the conjunctiva, retina and optic nerve may be involved in this disease process than can impair vision. ENT manifestations include sudden deafness, tinnitus, and vertigo. Pulmonary manifestations include chronic cough, dyspnea on exertion, and wheezing. PFT may show obstructive pattern. Sputum may show typical Fabry lamellar inclusions; if disease is extensively involved lung parenchyma. Bronchoscopy or lung biopsy may be required to rule out other etiologies.

One study suggest that, life expectancy in this disease for males was 58.2 years, compared with 74.7 years and for females 75.4 years compared with 80.0 years in the general population, in which most common cause of death was cardiovascular disease. [11] Diagnosis is done by clinical presentation and by leukocyte α-galactosidase activity. Genetic analyses include GLA gene is the most accurate method of diagnosis. Urine sediment shows cells containing lipid globules called Maltese crosses. Definite treatment is enzyme replacement therapy. Fabrazyme is enzyme was approved by the Food and Drug Administration and these enzymes have a positive effect in early phase of disease especially on renal and cardiac manifestations, however, long term benefits especially regarding prevention of premature stroke is unclear. [12],[13],[14],[15]

We are not able to perform leukocyte α-galactosidase activity and genetic analysis, as this test is not available in our hospital and patient is not able to do this test, as it was very costly. We only suspect the disease based upon clinical presentation:

  1. Cutaneous manifestations,
  2. Autonomic dysfunction,
  3. Cardiac manifestations,
  4. Oral mucosal lesions,
  5. Raynaud's phenomenon, and some supportive laboratory investigations like derange renal functions and skin biopsy.

  Conclusion Top

In this case, clinical history and investigations were consistent with the diagnosis of Fabry's. We are reporting this rare manifestation.

  References Top

William JD, Timothy BG, Dirk E. Andrews' Diseases of the Skin: clinical Dermatology. Philadelphia: Saunders Elsevier; 2006. p. 538.  Back to cited text no. 1
Hurwitz S. Inborn errors of metabolism. Clinical Pediatric Dermatology. 3 rd ed. Philadelphia: W.B. Saunders; 2003.  Back to cited text no. 2
Desnick RJ, Banikazemi M. Fabry disease: alpha-galactosidase a deficiency (Angiokeratoma Corporis Diffusum Universale). Fitzpatrick's Dermatology in General Medicine. 6 th ed. New York: McGraw-Hill; 2003.  Back to cited text no. 3
Möhrenschlager M, Braun-Falco M, Ring J, Abeck D. Fabry disease: Recognition and management of cutaneous manifestations. Am J Clin Dermatol 2003;4:189-96.  Back to cited text no. 4
Chimenti C, Pieroni M, Morgante E, Antuzzi D, Russo A, Russo MA, et al. Prevalence of Fabry disease in female patients with late-onset hypertrophic cardiomyopathy. Circulation 2004;110:1047-53.  Back to cited text no. 5
Linhart A, Palecek T, Bultas J, Ferguson JJ, Hrudová J, Karetová D, et al. New insights in cardiac structural changes in patients with Fabry's disease. Am Heart J 2000;139:1101-8.  Back to cited text no. 6
Ries M, Ramaswami U, Parini R, Lindblad B, Whybra C, Willers I, et al. The early clinical phenotype of Fabry disease: A study on 35 European children and adolescents. Eur J Pediatr 2003;162:767-72.  Back to cited text no. 7
Sessa A, Meroni M, Battini G, Maglio A, Brambilla PL, Bertella M, et al. Renal pathological changes in Fabry disease. J Inherit Metab Dis 2001;24 (Suppl 2):66-70.  Back to cited text no. 8
Mitsias P, Levine SR. Cerebrovascular complications of Fabry's disease. Ann Neurol 1996;40:8-17.  Back to cited text no. 9
Sher NA, Reiff W, Letson RD, Desnick RJ. Central retinal artery occlusion complicating Fabry's disease. Arch Ophthalmol 1978;96:815-7.  Back to cited text no. 10
Waldek S, Patel MR, Banikazemi M, Lemay R, Lee P. Life expectancy and cause of death in males and females with Fabry disease: Findings from the Fabry Registry. Genet Med 2009;11:790-6.  Back to cited text no. 11
Lidove O, Joly D, Barbey F, Bekri S, Alexandra JF, Peigne V, et al. Clinical results of enzyme replacement therapy in Fabry disease: A comprehensive review of literature. Int J Clin Pract 2007;61:293-302.  Back to cited text no. 12
Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, et al. Safety and efficacy of recombinant human alpha-galactosidase A - replacement therapy in Fabry's disease. N Engl J Med 2001;345:9-16.  Back to cited text no. 13
Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet 2004;75:65-74.  Back to cited text no. 14
Moore DF, Scott LT, Gladwin MT, Altarescu G, Kaneski C, Suzuki K, et al. Regional cerebral hyperperfusion and nitric oxide pathway dysregulation in Fabry disease: Reversal by enzyme replacement therapy. Circulation 2001;104:1506-12.  Back to cited text no. 15


  [Figure 1], [Figure 2]


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