Question

What metabolic defect results from impairment of the enzyme homogentisate oxidase in the tyrosine catabolic pathway? Please explain the defect and common symptoms.

Answer 1

Alkaptonuria is caused by a mutation on your homogentisate 1,2-dioxygenase (HGD) gene. It's an autosomally recessive condition.It is a metabolic disease characterized by the accumulation of homogentisic acid and its oxidized product, benzoquinone acetic acid , in various tissues (e.g. cartilage, connective tissue) and body fluids (urine, sweat), causing urine to darken when exposed to air as well as grey-blue coloration of the sclera and ear helix (ochronosis), and a disabling joint disease involving both the axial and peripheral joints (ochronotic arthropathy).

Dark stains on a baby’s diaper are one of the earliest signs of alkaptonuria. There are few other symptoms during childhood.

Symptoms become more obvious as you age. Your urine may turn dark brown or black when it’s exposed to air. By the time you reach your 20s or 30s, you may notice signs of early-onset osteoarthritis.

Other symptoms-

• dark spots in the sclera (white) of your eyes
• thickened and darkened cartilage in your ears
• blue speckled discoloration of your skin, particularly around sweat glands
• dark-colored sweat or sweat stains
• black earwax
• kidney stones and prostate stones
• arthritis (especially hip and knee joints)

Alkaptonuria can also lead to heart problems.