Fabry's disease; angiokeratoma corporis diffusum
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Introduction
X-linked recessive inborn error of metabolism.
Etiology
- deficiency in alpha-galactosidase A (ceramide trihexosidase)
Epidemiology
rare (young men)
Pathology
- deficiency in alpha-galactosidase A leads to accumulation of neutral glycosphingolipid ceramide trihexoside (globotriaoslyceramide) in lysosomes of:
- coronary artery disease
- cerebrovascular disease
Genetics
- X-linked recessive
- associated with defects in alpha-galactosidase A (GLA)
Clinical manifestations
- numerous dark, red, punctate & tiny (< 1 mm) angiokeratoma on lower 1/2 of the body
- lower abdomen
- genitalia
- buttocks
- lesions may occur on lips
- lesions generally develop during childhood & adolescence
- telangiectasias[4]
- kidney failure (renal insufficiency)
- neuropathic pain in lower extremities
- acroparesthesias (painful paresthesias of the hands)
- transient ischemic attacks
- myocardial infarction, premature coronary artery disease
- corneal opacities (corneal dystrophy)
- present in 90% of patients
- heterozygous females may have corneal opacities
- frequent postprandial bowel movements
- hypohidrosis
Laboratory
- urinalysis
- urine protein: mild proteinuria
- excess ceramide trihexoside in urine
- renal function tests
- GLA gene mutation
Complications
Management
- enzyme replacement (Replagal or Fabrazyme) is effective[4]
- carbamazepine or phenytoin may be useful for acroparethesias
- metoclopramide or Lipisorb for GI hypermotility.
- prognosis: survival into adulthood is common
- screening for Fabry's disease is recommended for family members of affected patients[4]
More general terms
Additional terms
- acroparesthesia
- alpha-galactosidase A (ceramide trihexosidase, melibiase, GLA)
- angiokeratoma
- chronic renal failure (CRF)
- myocardial infarction (MI); heart attack
References
- ↑ Textbook of Biochemistry with Clinical Correlations, 3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 459
- ↑ Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 159
- ↑ Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 175
- ↑ 4.0 4.1 4.2 4.3 Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18. American College of Physicians, Philadelphia 2009, 2012, 2018.
- ↑ Laney DA, Bennett RL, Clarke V et al Fabry disease practice guidelines: recommendations of the National Society of Genetic Counselors. J Genet Couns. 2013 Oct;22(5):555-64. PMID: https://www.ncbi.nlm.nih.gov/pubmed/23860966
- ↑ Feriozzi S, Torras J, Cybulla M et al The effectiveness of long-term agalsidase alfa therapy in the treatment of Fabry nephropathy. Clin J Am Soc Nephrol. 2012 Jan;7(1):60-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/22246281 Free PMC Article
- ↑ Pisani A, Visciano B, Imbriaco M et al The kidney in Fabry's disease. Clin Genet. 2014 Oct;86(4):301-9. PMID: https://www.ncbi.nlm.nih.gov/pubmed/24645664
- ↑ NINDS Fabry's Disease Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Fabry-Disease-Information-Page
Patient information
Fabry's disease patient information