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calcification","onset_id":null,"reference":"OMIM:203500","source_release":"2026-06-23"},"sourceGroups":["omim"]}],"referenceLabels":{},"references":{"causeHtml":"<ul><li><a href=\"https://medlineplus.gov/genetics/condition/alkaptonuria\">Alkaptonuria</a></li></ul>","identityNote":"MONDO cross-references identify native condition entries. Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"<p>Variants (also called mutations) in the HGD gene cause alkaptonuria. The HGD gene provides instructions for making an enzyme called homogentisate 1,2-dioxygenase. This enzyme helps break down the amino acids phenylalanine and tyrosine, which are important building blocks of proteins. Phenylalanine and tyrosine are broken down when they are no longer needed or when there are too many of them.</p><p>Variants in the HGD gene cause the cell to produce a version of the enzyme that does not function well. As a result, phenylalanine and tyrosine are not completely broken down. Instead, a substance called homogentisic acid, which is produced during the breakdown process, accumulates in the body.</p><p>Excess homogentisic acid settles in connective tissues, forming a substance called ochronotic pigment, which causes cartilage and skin to darken. Over time, a buildup of this pigment calcifies, leading to many of the health problems seen in people with alkaptonuria. Excess homogentisic acid is also excreted in urine, making urine turn dark when exposed to air.</p><p class=\"section-source\"><a href=\"https://medlineplus.gov/genetics/condition/alkaptonuria/#causes\">MedlinePlus Genetics: Causes</a></p>","key":"forms","title":"What causes Alkaptonuria?"},{"bodyHtml":"<p>Ochronosis occurs in connective tissues throughout the body, such as the joints, tendons, and ligaments. Pigment changes can be easily seen in the whites of the eyes (sclera), the outer ears, and the hands. Dark pigment can also be found in earwax and in body sweat (perspiration). These pigment changes are usually evident after age 30.</p><p>Ochronosis in the joints causes people with alkaptonuria to develop arthritis, typically in early adulthood. Arthritis usually affects the spine and large joints (such as the hips and knees). Many affected individuals require joint replacements later in life.</p><p>Over time, the deposits of pigment can harden (calcify). Calcification in joints or ligaments causes them to become rigid and brittle, decreasing their flexibility and making them prone to damage. Calcification of the discs that separate the bones of the spine can cause further back pain. This calcification can also affect the cartilage that makes up the valves of the heart, which allow blood to move through the heart and prevent blood from flowing backward. As a result, the heart valves narrow (stenosis), which can cause the valves to leak (regurgitation).</p><p>The body removes the excess pigment in urine. However, removing the large pigment deposits found in people with alkaptonuria can put strain on the kidneys, and this can lead to kidney (renal) failure. Similarly, a buildup of these substances in the kidneys or prostate gland can cause calcium stones to develop. If the body cannot effectively process and remove the pigment and related substances, these products substances can continue to build up in the body, worsening ochronosis, arthritis, and other features of alkaptonuria.</p><p>With appropriate medical management, people with alkaptonuria generally have a normal life expectancy.</p><p class=\"section-source\">Source: <a href=\"https://medlineplus.gov/genetics/condition/alkaptonuria\">MedlinePlus Genetics</a></p>","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"alkaptonuria","sourceDocuments":[{"name":"Alkaptonuria","reviewed":"2025-03","sections":{"causes":{"fetchedAt":"2026-10-20T20:19:14.987395+00:00","label":"Causes","pageSha256":"81fe5277842a39b36f6bca8176d160bcea716870540f588576e286adc1349804","sourceUrl":"https://medlineplus.gov/genetics/condition/alkaptonuria/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/alkaptonuria"}],"sourceNote":"MedlinePlus descriptions and Causes; original HPO annotations.","takeawayHtml":"Cause explanations are from MedlinePlus Genetics. Feature values below retain their original sources and patient groups.","title":"Alkaptonuria"},"schemaVersion":1}