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Ancestor membership does not transfer phenotype values between groups.","importantHtml":""},"sections":[{"bodyHtml":"<p>Hyperprolinemia is caused by variants (also known as mutations) in the ALDH4A1 and PRODH genes. These genes provide instructions for enzymes that break down proline.</p><p>Hyperprolinemia type I is caused by variants in the PRODH gene, which provides instructions for producing an enzyme called proline dehydrogenase. This enzyme begins the process of breaking down proline by starting the reaction that converts proline to pyrroline-5-carboxylate.</p><p>Hyperprolinemia type II is caused by variants in the ALDH4A1 gene, which provides instructions for producing the enzyme pyrroline-5-carboxylate dehydrogenase. This enzyme helps to break down the pyrroline-5-carboxylate produced in the previous reaction, converting it to the amino acid glutamate.</p><p>The conversion of proline to glutamate (and the conversion of glutamate to proline, which is controlled by different enzymes) is important for maintaining a supply of amino acids needed for protein production, and for energy transfer within the cell.</p><p>Variants in either the PRODH or ALDH4A1 gene can cause a reduction in proline dehydrogenase or pyrroline-5-carboxylate dehydrogenase function and a decrease in the breakdown of proline. As a result, there is a buildup of proline in the body, leading to hyperprolinemia.</p><p class=\"section-source\"><a href=\"https://medlineplus.gov/genetics/condition/hyperprolinemia/#causes\">MedlinePlus Genetics: Causes</a></p>","key":"forms","title":"What causes Hyperprolinemia?"},{"bodyHtml":"<p>People with hyperprolinemia type I often do not show any symptoms, although they have proline levels in their blood between 3 and 10 times the normal level. Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems.</p><p>Hyperprolinemia type II results in proline levels in the blood between 10 and 15 times higher than normal, and high levels of a related compound called pyrroline-5-carboxylate. This form of the disorder is more likely than type I to involve seizures or intellectual disability that vary in severity.</p><p>Hyperprolinemia can also occur with other conditions, such as malnutrition or liver disease. In particular, individuals with conditions that cause elevated levels of a chemical called lactic acid in the blood (lactic acidosis) may have hyperprolinemia as well, because lactic acid stops (inhibits) the breakdown of proline.</p><p class=\"section-source\">Source: <a href=\"https://medlineplus.gov/genetics/condition/hyperprolinemia\">MedlinePlus Genetics</a></p>","key":"overview","title":"Condition overview"}],"sharedSources":[],"slug":"hyperprolinemia","sourceDocuments":[{"name":"Hyperprolinemia","reviewed":"2007-06","sections":{"causes":{"fetchedAt":"2026-10-20T20:22:20.539277+00:00","label":"Causes","pageSha256":"2d8218ee35f9f184940d9a141fc3bc664643e168f5d007ba13a063a90e768894","sourceUrl":"https://medlineplus.gov/genetics/condition/hyperprolinemia/#causes","status":"available"}},"source_release":"2026-10-01","url":"https://medlineplus.gov/genetics/condition/hyperprolinemia"}],"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":"Hyperprolinemia"},"schemaVersion":1}