autosomal recessive hypophosphatemic rickets

Autosomal Recessive Hypophosphatemic Rickets (ARHR) is a rare genetic disorder characterized by defective bone mineralization and renal phosphate wasting due to a loss-of-function mutation in the ENPP1 gene [8][9]. This condition leads to low levels of phosphate in the blood (hypophosphatemia), resulting in rickets, bone pain, and short stature [2][6].

The symptoms of ARHR can vary in severity but may include:

• Rickets: a softening of bones that can cause bowing of the legs
• Bone pain: due to defective bone mineralization
• Short stature: as a result of poor bone growth
• Joint pain: associated with the condition

ARHR is caused by a homozygous mutation in the ENPP1 gene, which codes for an enzyme involved in phosphate metabolism [8]. This genetic defect leads to impaired renal phosphate reabsorption, resulting in hypophosphatemia and subsequent rickets.

It's worth noting that ARHR is a rare condition, and its symptoms can be similar to those of other bone disorders. A proper diagnosis by a medical professional is essential for accurate identification and treatment of the condition.

Autosomal Recessive Hypophosphatemic Rickets (ARHR2) presents with a range of symptoms, which can vary in severity from one individual to another.

Common Signs and Symptoms:

• Bone deformity [1]
• Bone pain [1]
• Increased risk of bone fractures [1]
• Short stature [1]

These symptoms often become apparent during early childhood. In some cases, the signs and symptoms may not manifest until adolescence or adulthood.

Additional Findings:

• Fatigue [3]
• Muscle weakness [3]
• Repeated bone fractures [3]

The disease can also present as a spectrum of abnormalities, ranging from mild hypophosphatemia to severe rickets or osteomalacia. In more severe cases, symptoms may include:

• Bowed legs or knock knees [2]
• Poor bone growth
• Short stature
• Joint and bone pain [5]

Variations in Presentation:

The signs and symptoms of ARHR2 can vary widely among individuals. In most cases, the features begin to manifest during early childhood. However, when the disease presents during adolescence or adulthood, clinical findings may include:

• Bone pain
• Muscle weakness
• Pseudo fractures [8]

In some instances, particularly in boys, the features are more severe and may include short stature, prominent bowing of the legs, and rachitic signs [9].

References: [1] - Context result 1: May 17, 2023 — Signs & Symptoms. Bone deformity, bone pain, increased risk of bone fractures and short stature are symptoms of ARHR2. [2] - Context result 2: Sep 1, 2010 — The most noticeable of these abnormalities are bowed legs or knock knees. [3] - Context result 3: Additional findings may include fatigue, muscle weakness and repeated bone fractures. [5] - Context result 5: Severe forms may be linked to bowing of the legs, poor bone growth, and short stature as well as joint and bone pain. Hypophosphatemic rickets are associated ... [8] - Context result 8: When the disease manifests during adolescence or adulthood, clinical findings include bone pain, muscle weakness, and pseudo fractures. [9] - Context result 9: The features are usually more severe in boys and include short stature, prominent bowing of the legs, and, sometimes, rachitic signs.

Autosomal Recessive Hypophosphatemic Rickets (ARHR) is a rare genetic disorder characterized by low levels of phosphate in the blood, leading to various skeletal and dental abnormalities. Diagnostic tests for ARHR are crucial for early detection and management of the condition.

Biochemical Tests

• Biochemical tests reveal hypophosphatemia (low phosphate levels) in the blood, which confirms a genetic diagnosis of autosomal recessive hypophosphatemic rickets [6].
• Serum calcium, phosphate, and alkaline phosphatase levels are assessed to confirm the diagnosis [9].

Molecular Genetic Testing

• A 13-gene panel that includes assessment of non-coding variants is ideal for patients with a clinical suspicion of hypophosphatemic rickets [7].
• Molecular genetic testing confirms the diagnosis by identifying mutations in the SLC34A1 gene, which encodes for the sodium-phosphate cotransporter type IIa protein [3].

Radiological Findings

• Radiological findings include typical signs of rickets and/or osteomalacia, such as bowing of long bones, softening of bone, and delayed bone age [8].
• Imaging studies like X-rays, CT scans, and MRI can help identify these radiological features.

Other Diagnostic Tests

• Clinical laboratory evaluation begins with assessment of serum calcium, phosphate, and alkaline phosphatase levels [9].
• A comprehensive diagnostic workup may include a 13-gene panel for patients with a clinical suspicion of hypophosphatemic rickets [7].

It's essential to note that the diagnosis of ARHR relies on the combination of clinical, radiographic, biochemical, and genetic features [3]. A multidisciplinary approach involving pediatricians, endocrinologists, and geneticists is often necessary for accurate diagnosis and management.

References: [3] by MR Laurent · 2021 · Cited by 51 — The diagnosis of XLH relies on the combination of clinical, radiographic, biochemical and genetic features (25). [6] by D Chaturvedi · 2024 — Biochemical tests revealed hypophosphatemia (0.71 mmol/L ... (Tyr374*)) confirming a genetic diagnosis of autosomal recessive hypophosphatemic rickets. [7] Nov 13, 2023 — A 13 gene panel that includes assessment of non-coding variants. Is ideal for patients with a clinical suspicion of hypophosphatemic rickets. [8] Radiological findings include typical signs of rickets and/or osteomalacia. Molecular genetic testing confirms the diagnosis. Differential diagnosis. [9] Aug 20, 2024 — Begin clinical laboratory evaluation of rickets with assessment of serum calcium, phosphate, and alkaline phosphatase levels. In ...

Treatment Options for Autosomal Recessive Hypophosphatemic Rickets

Autosomal recessive hypophosphatemic rickets (ARHR) is a rare genetic disorder characterized by impaired bone mineralization due to excessive production of fibroblast growth factor 23 (FGF23). While there is no cure for ARHR, various treatment options can help manage the condition and alleviate symptoms.

Phosphate Supplementation

One of the primary treatments for ARHR is phosphate supplementation. This involves administering neutral phosphate solution or tablets to

The differential diagnosis for autosomal recessive hypophosphatemic rickets (ARHR) includes several conditions that present with similar symptoms and characteristics.

• X-linked hypophosphatemia (XLH): This is a genetic disorder caused by mutations in the PHEX gene, leading to impaired phosphate reabsorption in the kidneys. Like ARHR, XLH presents with low phosphate levels, rickets, or osteomalacia [1].
• Autosomal dominant hypophosphatemic rickets (ADHR): This is another genetic disorder caused by mutations in the FGF23 gene, leading to impaired phosphate reabsorption in the kidneys. ADHR also presents with low phosphate levels, rickets, or osteomalacia [2].
• Hereditary hypophosphatemic rickets with hypercalciuria (HHRH): This is a rare genetic disorder caused by mutations in the SLC34A1 gene, leading to impaired phosphate reabsorption and excessive calcium excretion in the kidneys. Like ARHR, HHRH presents with low phosphate levels, rickets, or osteomalacia [3].
• Other conditions: Differential diagnosis also includes other conditions that may present with similar symptoms, such as vitamin D deficiency, thyroid disorders, and certain medications.

It's essential to note that a comprehensive diagnostic workup is necessary to accurately diagnose ARHR and differentiate it from these other conditions. This may involve genetic testing, biochemical analysis, and radiological imaging [4].

References:

[1] - Context result 5 [2] - Context result 9 [3] - Context result 6 [4] - Context result 9