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Fabry's disease; angiokeratoma corporis diffusum

X-linked recessive inborn error of metabolism. Etiology: - deficiency in alpha-galactosidase A (ceramide trihexosidase) Epidemiology: rare (young men) Pathology: 1) deficiency in alpha-galactosidase A leads to accumulation of neutral glycosphingolipid ceramide trihexoside (globotriaoslyceramide) in lysosomes of: a) endothelial cells b) fibrocytes c) pericytes in the 1] dermis 2] heart 3] kidneys 4] autonomic nervous system 2) coronary artery disease 3) cerebrovascular disease Genetics: - X-linked recessive - associated with defects in alpha-galactosidase A (GLA) Clinical manifestations: 1) numerous dark, red, punctate & tiny (< 1 mm) angiokeratoma on lower 1/2 of the body a) lower abdomen b) genitalia c) buttocks d) lesions may occur on lips e) lesions generally develop during childhood & adolescence 2) telangiectasias [4] 3) kidney failure (renal insufficiency) 4) neuropathic pain in lower extremities 5) acroparesthesias (painful paresthesias of the hands) 6) transient ischemic attacks 7) myocardial infarction, premature coronary artery disease 8) corneal opacities (corneal dystrophy) a) present in 90% of patients b) heterozygous females may have corneal opacities 9) frequent postprandial bowel movements 10) hypohidrosis Laboratory: - urinalysis - proteinuria - isosthenuria - urine protein: mild proteinuria - excess ceramide trihexoside in urine - renal function tests a) serum creatinine b) serum urea nitrogen c) creatinine clearance - GLA gene mutation Complications: 1) stroke 2) myocardial infarction 3) renal insufficiency Management: 1) enzyme replacement (Replagal or Fabrazyme) is effective [4] - Elfabrio FDA-approved May 2023 2) carbamazepine or phenytoin may be useful for acroparethesias 3) metoclopramide or Lipisorb for GI hypermotility. 4) prognosis: survival into adulthood is common 5) screening for Fabry's disease is recommended for family members of affected patients [4]

Related

acroparesthesia alpha-galactosidase A (ceramide trihexosidase, melibiase, GLA) angiokeratoma chronic renal failure (CRF) myocardial infarction (MI); heart attack

General

sphingolipidosis; sphingolipodystrophy; cerebral lipidosis X-linked disease

Properties

ACCUMULATION: ceramide galatosyllactoside DEFICIENCY: alpha-galactosidase A

Database Correlations

OMIM correlations MORBIDMAP 300644

References

  1. Textbook of Biochemistry with Clinical Correlations, 3rd ed., TM Devlin (ed), Wiley-Liss, NY 1992 pg 459
  2. Color Atlas and Synopsis of Clinical Dermatology, Common and Serious Diseases, 3rd ed, Fitzpatrick et al, McGraw Hill, NY, 1997, pg 159
  3. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 175
  4. Medical Knowledge Self Assessment Program (MKSAP) 15, 16, 18. American College of Physicians, Philadelphia 2009, 2012, 2018.
  5. 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: 23860966
  6. 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: 22246281 Free PMC Article
  7. Pisani A, Visciano B, Imbriaco M et al The kidney in Fabry's disease. Clin Genet. 2014 Oct;86(4):301-9. PMID: 24645664
  8. NINDS Fabry's Disease Information Page https://www.ninds.nih.gov/Disorders/All-Disorders/Fabry-Disease-Information-Page