IllnessAlkaptonuria, differential diagnosis

NGS +

Alkaptonuria is caused by a deficiency/dysfunction of homogentisate-1,2-dioxygenase, an enzyme that converts homogentisic acid (HGA) into maleylacetoacetic acid in the tyrosine degradation pathway. Pathogenic variants in the HGD gene (homogentisate 1,2-dioxygenase gene) are the cause. The disease is inherited in an autosomal recessive manner. The three main features of alkaptonuria are dark urine or urine that turns dark when standing, ochronosis (bluish-black pigmentation in the connective tissue) and arthritis of the spine and larger joints. Ochronosis usually occurs after the age of 30; arthritis often begins in the third decade of life. Other manifestations may include: gray-blue pigmentation of the sclerae, pigmentation of the ear cartilage and skin of the hands; calcification or regurgitation of the aortic or mitral valve and occasionally aortic dilatation; kidney stones; stones of the prostate; and hypothyroidism. (according to gene reviews: https://www.ncbi.nlm.nih.gov/books/NBK1454)

In addition to the HGD gene, three other genes that may be the cause of similar symptoms are examined in this panel.

An normal result does not rule out a genetic cause of the symptoms.

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• Alias: Black urine disease
• Alias: Homogentisate 1,2-dioxygenase deficiency
• Alias: Ochronose
• Alkaptonuria (HGD)
• Cardiac valvular dysplasia, XL (FLNA)
• Porphyria, acute hepatic (ALAD)
• Porphyria, acute intermittent (HMBS)
• Porphyria, acute intermittent, nonerythroid variant (HMBS)