Alcaptonuria

Alkaptonuria Alkaptonuria is a rare genetic disorder characterized by the accumulation of homogentisic acid in the body, leading to a range of symptoms and complications. This condition is inherited in an autosomal recessive pattern and is caused by mutations in the HGD gene.

Pathophysiology

Alkaptonuria results from a deficiency of the enzyme homogentisate 1,2-dioxygenase, which is responsible for breaking down homogentisic acid, an intermediate in the metabolism of the amino acids phenylalanine and tyrosine. The accumulation of homogentisic acid leads to its deposition in connective tissues, a condition known as ochronosis, and is excreted in urine, causing it to darken upon standing.

Clinical Features

The clinical manifestations of alkaptonuria can vary but typically include:

• Dark Urine: One of the earliest signs, often noticed in infancy, is the darkening of urine when exposed to air.
• Ochronosis: This refers to the bluish-black discoloration of connective tissues, particularly noticeable in the ear cartilage and sclera of the eyes.
• Arthropathy: Patients often develop arthritis, particularly in the spine and large joints, due to the deposition of homogentisic acid in cartilage.
• Cardiovascular Complications: There can be calcification of heart valves and coronary arteries.

Diagnosis

Diagnosis of alkaptonuria is based on clinical features and confirmed by:

• Urine Analysis: Detection of elevated levels of homogentisic acid in the urine.
• Genetic Testing: Identification of mutations in the HGD gene.

Management

There is currently no cure for alkaptonuria, but management focuses on alleviating symptoms and preventing complications:

• Dietary Restrictions: Limiting intake of phenylalanine and tyrosine may reduce homogentisic acid levels.
• Pain Management: Use of analgesics and anti-inflammatory medications to manage joint pain.
• Physical Therapy: To maintain joint function and mobility.
• Surgical Interventions: Joint replacement surgery may be necessary in severe cases of arthritis.

Research and Future Directions

Research is ongoing to find more effective treatments for alkaptonuria. Enzyme replacement therapy and gene therapy are potential future approaches.

See Also

• Ochronosis
• Genetic Disorders
• Metabolic Pathways

,

 Natural history of alkaptonuria, 
 New England Journal of Medicine, 
 2002, 
 Vol. 347(Issue: 26), 
 pp. 2111-2121, 
 DOI: 10.1056/NEJMoa021736,

,

 The Metabolic and Molecular Bases of Inherited Disease, 
  
 McGraw-Hill, 
 2001, 
  
  
 ISBN 978-0079130358,

NIH genetic and rare disease info

• NIH info on Alcaptonuria

Alcaptonuria is a rare disease.