Related Experiment Video
Updated: Jul 7, 2026
07:13
Two Techniques to Create Hypoparathyroid Mice: Parathyroidectomy Using GFP Glands and Diphtheria-Toxin-Mediated Parathyroid Ablation
Published on: March 14, 2017
A translocation causing increased alpha-klotho level results in hypophosphatemic rickets and hyperparathyroidism
Catherine A Brownstein1, Felix Adler, Carol Nelson-Williams
1Department of Genetics, Howard Hughes Medical Institute, Yale University School of Medicine, New Haven, CT 06510.
Summary
This study identifies a new syndrome linking hypophosphatemic rickets and hyperparathyroidism to a genetic translocation affecting alpha-Klotho. Elevated alpha-Klotho may mimic hyperphosphatemia responses, impacting phosphate and parathyroid regulation.
Area of Science:
- Endocrinology
- Genetics
- Mineral Metabolism
Background:
- Phosphate homeostasis is crucial for energy, bone, and cell membrane formation.
- Disruptions lead to hypophosphatemic rickets (low phosphate) or hyperphosphatemia (high phosphate) seen in renal failure.
- Hyperphosphatemia is linked to parathyroid hyperplasia and renal osteodystrophy.
Observation:
- A novel syndrome presents with hypophosphatemic rickets, hyperparathyroidism, and parathyroid hyperplasia.
- This condition arises from a de novo translocation near the alpha-Klotho gene.
- Affected patients exhibit increased plasma alpha-Klotho and beta-glucuronidase activity, with elevated FGF23.
Findings:
- The alpha-Klotho gene translocation is identified as the cause of this syndrome.
- Elevated alpha-Klotho levels appear to mimic the body's response to high phosphate.
- Alpha-Klotho plays a role in regulating phosphate levels and parathyroid gland size and function.
Implications:
- This research highlights alpha-Klotho's role in phosphate balance and parathyroid regulation.
- Findings offer insights into the pathogenesis of renal osteodystrophy.
- Potential therapeutic strategies for renal osteodystrophy may emerge from understanding alpha-Klotho's function.
Related Concept Videos
01:17Hormones and Bone Tissue
The endocrine system produces and secretes hormones, which interact with the skeletal system. These hormones control bone growth, maintain bone once it is formed, and remodel it.
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
Hormones That Influence Osteoblasts and/or Maintain the Matrix
Several hormones are necessary for controlling bone growth and maintaining the bone matrix. The pituitary gland secretes growth hormone (GH), which, as its name implies, controls bone growth. This happens in several ways: first, it triggers chondrocyte...
01:27Hyperthyroidism II: Pathophysiology
Hyperthyroidism is a hypermetabolic state caused by elevated levels of thyroid hormones, triiodothyronine (T3) and thyroxine (T4). It results from dysregulation at the thyroid, pituitary, or immune system level and affects multiple organ systems.PathophysiologyThe most common cause of hyperthyroidism is Graves’ disease, an autoimmune disorder in which antibodies, specifically thyroid-stimulating antibodies (TSAb), a subtype of TSH receptor antibodies (TRAb), bind to and activate TSH receptors...
01:21Skeleton and Calcium Homeostasis
Calcium is not only the most abundant mineral in bone but also the most abundant mineral in the human body. Calcium ions are needed for bone mineralization, tooth health, heart rate regulation and strength of contraction, blood coagulation, the contraction of smooth and skeletal muscle cells, and the regulation of nerve impulse conduction. The average calcium level in the blood is about 10 mg/dL. When the body cannot maintain this level, a person will experience hypo or hypercalcemia.
01:24Graves Disease II: Pathophysiology
Graves’ disease is an autoimmune disorder characterized by the production of thyroid-stimulating immunoglobulins (TSI) that activate TSH receptors, leading to excessive synthesis and release of thyroid hormones (T3 and T4) and resulting in hyperthyroidism.Among all causes of hyperthyroidism, Graves’ disease is the most common and can happen at any age, though it is more frequent in women. It produces a hypermetabolic state with features such as weight loss, tachycardia, tremor, and heat...
00:59The Parathyroid Glands
The two pairs of parathyroid glands embedded within the posterior surface of the thyroid gland are restricted by a dense capsule around them. These glands comprise two distinct cell populations—parathyroid oxyphil and parathyroid principal cells- pivotal in calcium homeostasis.
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...
Oxyphil cells, whose functions remain elusive, emerge during late puberty, adding a layer of complexity to the parathyroid gland's intricacies. In contrast, principal parathyroid cells undertake a vital role by producing...
01:24Chronic Kidney Disease II: Clinical Manifestations
Chronic Kidney Disease (CKD) progressively impairs multiple body systems due to the accumulation of uremic toxins, which disrupt cellular functions across various organs.Neurologic symptomsNeurologic symptoms often arise early in CKD, as uremic toxin buildup drives changes in cognitive and motor functions. Patients frequently experience fatigue, headache, confusion, difficulty concentrating, and, in severe cases, seizures. Peripheral neuropathy commonly manifests as burning sensations in the...