{"id":4422555,"date":"2025-01-12T05:26:50","date_gmt":"2025-01-12T11:26:50","guid":{"rendered":"https:\/\/myendoconsult.com\/learn\/topics\/hypophosphatasia\/"},"modified":"2025-01-13T06:21:06","modified_gmt":"2025-01-13T12:21:06","slug":"hypophosphatasia","status":"publish","type":"oen_topic","link":"https:\/\/myendoconsult.com\/learn\/topics\/hypophosphatasia\/","title":{"rendered":"Hypophosphatasia"},"content":{"rendered":"\n<h2 class=\"wp-block-heading\">HYPOPHOSPHATASIA<\/h2>\n\n\n\n<h3 class=\"wp-block-heading\">Definition and Background<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Rare inherited<\/strong> disorder characterized by <strong>low alkaline phosphatase<\/strong> levels in serum and bone.<\/li>\n\n\n\n<li>Results in <strong>defective bone<\/strong> and <strong>tooth mineralization<\/strong>, leading to osteomalacia and severe periodontal disease.<\/li>\n\n\n\n<li>Caused by <strong>mutations<\/strong> in the <strong>ALPL gene<\/strong> (tissue-nonspecific alkaline phosphatase isoenzyme).<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Inheritance and Clinical Variants<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Perinatal<\/strong> and <strong>infantile<\/strong> forms: usually <strong>autosomal recessive<\/strong>.<\/li>\n\n\n\n<li><strong>Milder forms<\/strong> (childhood or adulthood): can be <strong>autosomal dominant<\/strong> or <strong>autosomal recessive<\/strong>, depending on specific gene mutations.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Perinatal Lethal Hypophosphatasia<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Complete absence<\/strong> of alkaline phosphatase; <strong>estimated prevalence<\/strong>: ~1 in 100,000 births.<\/li>\n\n\n\n<li>Severe manifestations:\n<ul class=\"wp-block-list\">\n<li>Lack of mineralized bone <strong>in utero<\/strong> \u2192 profound skeletal deformities.<\/li>\n\n\n\n<li><strong>Skin-covered osteochondral spurs<\/strong> on legs and forearms.<\/li>\n\n\n\n<li><strong>Rachitic chest<\/strong> deformities, <strong>hypoplastic lungs<\/strong> (respiratory compromise).<\/li>\n\n\n\n<li><strong>Premature craniosynostosis<\/strong> \u2192 \u2191 intracranial pressure.<\/li>\n\n\n\n<li>Seizures, <strong>hypercalcemia<\/strong>, <strong>nephrocalcinosis<\/strong>, and renal failure.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Typically <strong>fatal<\/strong> early.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Childhood Hypophosphatasia<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Results from <strong>milder ALPL<\/strong> mutations.<\/li>\n\n\n\n<li>Skeletal abnormalities include:\n<ul class=\"wp-block-list\">\n<li>Enlarged joints, focal metaphyseal changes, <a href=\"https:\/\/myendoconsult.com\/learn\/evaluation-of-short-stature\/\"  data-wpil-monitor-id=\"277\">short stature<\/a>.<\/li>\n\n\n\n<li>Premature loss of deciduous <strong>teeth<\/strong>, especially <strong>incisors<\/strong>.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Disease severity can fluctuate, sometimes improving spontaneously, then recurring later.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Adult-Onset Hypophosphatasia<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Often becomes symptomatic in <strong>4th\u20135th decade<\/strong> of life.<\/li>\n\n\n\n<li>Clinical features:\n<ul class=\"wp-block-list\">\n<li><strong>Thigh pain<\/strong> from femoral pseudofractures or metatarsal stress fractures.<\/li>\n\n\n\n<li><strong>Chondrocalcinosis<\/strong>.<\/li>\n\n\n\n<li><strong>Odontohypophosphatasia<\/strong>: severe dental caries, loose teeth, early tooth loss.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Pathophysiology<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li>Tissue-nonspecific alkaline phosphatase (TNAP) is needed to <strong>generate inorganic phosphate<\/strong> for hydroxyapatite formation.<\/li>\n\n\n\n<li>Mutations reduce TNAP enzyme activity \u2192 impaired bone mineralization.<\/li>\n\n\n\n<li><strong>Buildup of pyrophosphate<\/strong> also <strong>inhibits<\/strong> bone mineralization.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Laboratory Findings<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Low total alkaline phosphatase<\/strong> (ALP) in serum is a hallmark.<\/li>\n\n\n\n<li>Confirmed by <strong>increased<\/strong> blood and urine concentrations of <strong>organic phosphate compounds<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Phosphoethanolamine<\/li>\n\n\n\n<li>Phosphorylcholine<\/li>\n\n\n\n<li>Pyridoxal 5-phosphate<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Bone biopsy: same changes as other forms of rickets (unmineralized osteoid).<\/li>\n\n\n\n<li>Serum calcium and phosphorus are <strong>often normal<\/strong> in adults.<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Genetic Testing<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>Most ALPL mutations<\/strong> are missense; others include deletions, nonsense, or insertions.<\/li>\n\n\n\n<li>Disease severity correlates with <strong>residual enzyme<\/strong> activity:\n<ul class=\"wp-block-list\">\n<li><strong>Severe<\/strong> disease \u2192 negligible activity.<\/li>\n\n\n\n<li><strong>Mild<\/strong> disease \u2192 some preserved TNAP activity.<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n\n\n\n<h3 class=\"wp-block-heading\">Treatment<\/h3>\n\n\n\n<ul class=\"wp-block-list\">\n<li><strong>No current curative therapy<\/strong>.<\/li>\n\n\n\n<li>Management targets <strong>signs and symptoms<\/strong>:\n<ul class=\"wp-block-list\">\n<li>Bone pain, fractures, dental issues, etc.<\/li>\n<\/ul>\n<\/li>\n\n\n\n<li>Supportive care may involve orthopedic interventions, dental management, and sometimes experimental therapies.<\/li>\n<\/ul>\n","protected":false},"excerpt":{"rendered":"<p>HYPOPHOSPHATASIA Definition and Background Inheritance and Clinical Variants Perinatal Lethal Hypophosphatasia Childhood Hypophosphatasia Adult-Onset Hypophosphatasia Pathophysiology Laboratory Findings Genetic Testing Treatment<\/p>\n","protected":false},"featured_media":0,"template":"","oen_topic_chapter":[687],"class_list":["post-4422555","oen_topic","type-oen_topic","status-publish","hentry","oen_topic_chapter-parathyroid-gland","post-wrapper","thrv_wrapper"],"_links":{"self":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422555","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic"}],"about":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/types\/oen_topic"}],"version-history":[{"count":3,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422555\/revisions"}],"predecessor-version":[{"id":4422558,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic\/4422555\/revisions\/4422558"}],"wp:attachment":[{"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/media?parent=4422555"}],"wp:term":[{"taxonomy":"oen_topic_chapter","embeddable":true,"href":"https:\/\/myendoconsult.com\/learn\/wp-json\/wp\/v2\/oen_topic_chapter?post=4422555"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}