hereditary hypophosphatemic rickets with hypercalciuria

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by the excessive excretion of phosphate in the urine, leading to low phosphate levels in the blood (hypophosphatemia), and an increased level of calcium in the urine (hypercalciuria). This condition is associated with rickets or osteomalacia, which are bone disorders that cause softening and weakening of the bones.

Key Features:

• Hypophosphatemia: Low phosphate levels in the blood
• Hypercalciuria: Excessive excretion of calcium in the urine
• Rickets/Osteomalacia: Bone disorders causing softening and weakening of the bones

Causes: HHRH is caused by mutations in the SLC34A1 gene, which codes for a sodium-phosphate cotransporter responsible for phosphate reabsorption in the kidneys [7]. These mutations result in the development of urinary phosphate wasting and hypophosphatemic rickets, bowing, and short stature, as well as appropriately [1].

Symptoms:

• Short stature
• Bowing of the legs (genu varum)
• Rickets or osteomalacia
• Hypophosphatemia
• Hypercalciuria

References:

[1] Bergwitz et al. (2019) - These mutations result in the development of urinary phosphate (Pi) wasting and hypophosphatemic rickets, bowing, and short stature, as well as appropriately [1]. [2] Lorenz-Depiereux et al. (2006) - Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is an autosomal recessive form that is characterized by reduced renal phosphate reabsorption, [2] [7] Mejia-Gaviria et al. (2010) - Hereditary hypophosphatemic rickets with hypercalciuria is caused by loss-of-function in the type 2c sodium phosphate cotransporter encoded by [7].

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by impaired phosphate reabsorption in the kidneys, leading to low phosphate levels in the blood (hypophosphatemia). This condition can present with various signs and symptoms, including:

• Short stature: Affected individuals may experience growth delays or short stature [5].
• Muscle weakness: Muscle weakness is a common symptom of HHRH, which can be due to low phosphate levels affecting muscle function [5].
• Rickets or osteomalacia: This condition is characterized by softening and weakening of bones (rickets) in children or adults (osteomalacia), leading to bone pain and deformities [3].
• Bowed legs or knock knees: Weight-bearing activities can make these abnormalities more apparent [1].
• Premature fusion of skull bones (craniosynostosis): In some cases, affected individuals may experience premature closure of the skull bones, which can lead to abnormal head shapes and sizes [8].
• Dental abnormalities: HHRH can also cause dental problems, such as tooth decay or gum disease [8].
• Hair loss: Affected individuals may experience hair loss beginning in the first year of life, which can progress to total body hair loss (alopecia totalis) [9].

It's essential to note that not all affected individuals will exhibit all these symptoms, and the severity of the condition can vary from person to person. If you suspect someone has HHRH, it is crucial to consult a medical professional for proper diagnosis and treatment.

References: [1] - Context result 1 [3] - Context result 3 [5] - Context result 5 [8] - Context result 8 [9] - Context result 9

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by reduced renal phosphate reabsorption, leading to hypophosphatemia and hypercalciuria. Diagnostic tests for HHRH are crucial in establishing the correct diagnosis and differentiating this condition from other similar disorders.

Laboratory Investigations

• Blood tests: Vitamin D levels are typically elevated in HHRH patients [2]. Additionally, measuring FGF23 and PTH levels can be particularly useful in evaluating hypophosphatemia [2].
• Urine tests: High levels of calcium excretion (hypercalciuria) are a characteristic feature of HHRH [4].

Genetic Analysis

• A 13-gene panel that includes assessment of non-coding variants is ideal for patients with a clinical suspicion of hypophosphatemic rickets, including HHRH [3].
• Genetic analysis can help confirm the diagnosis and identify the underlying genetic mutation.

Imaging Studies

• Diagnostic imaging studies may be used to assess bone mineralization and detect any signs of rickets or osteomalacia. However, these tests are not specific for HHRH and should be used in conjunction with laboratory investigations and genetic analysis.

It's worth noting that a thorough clinical evaluation, including history, physical examination, and laboratory investigations, is essential in establishing the correct diagnosis of HHRH [9]. Genetic analysis can also play a crucial role in confirming the

Treatment Overview

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by impaired phosphate reabsorption in the kidneys, leading to low phosphate levels and high calcium levels in the blood. The treatment for HHRH focuses on correcting these imbalances.

Phosphate Supplementation

The primary treatment for HHRH involves long-term phosphorous supplementation [1][8]. This can lead to remission and rapid correction of biochemical abnormalities [1]. Phosphate supplements are essential to maintain normal phosphate levels in the blood, which is crucial for bone health and mineralization.

Vitamin D Analogues Contraindicated

Activated vitamin D analogues are contraindicated in HHRH because they can exacerbate hypercalciuria [4]. Instead, other treatment options should be considered to manage calcium levels and promote bone health.

Other Treatment Options

Treatment may also involve the use of neutral phosphate solution or tablets to lower ionized calcium concentrations [3]. In some cases, active forms of vitamin D combined with phosphate salts or anti-FGF23 antibody treatment might be used, depending on the underlying cause of HHRH [5].

It's essential to note that each individual's response to treatment may vary, and a comprehensive treatment plan should be tailored to their specific needs.

References: [1] Jul 9, 2020 — Currently, the only treatment for HHRH is long-term phosphorous supplementation which can singularly cause remission and rapid correction of ... [3] Treatment of hypophosphatemic rickets consists of neutral phosphate solution or tablets. Phosphate supplementation lowers ionized calcium concentrations and ... [4] Phosphate supplementation is the mainstay of treatment. It is important to note that activated vitamin D analogues are contraindicated in HHRH because they ... [5] by SA Ackah · 2023 · Cited by 27 — The treatment depends on the underlying cause, but often includes active forms of vitamin D combined with phosphate salts, or anti-FGF23 antibody treatment ( ...

Hereditary hypophosphatemic rickets with hypercalciuria (HHRH) is a rare genetic disorder characterized by impaired phosphate reabsorption in the kidneys, leading to excessive urinary excretion of phosphate and calcium. The differential diagnosis for H