hypophosphatemic nephrolithiasis/osteoporosis 2

Hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) is a rare genetic disorder characterized by decreased renal phosphate reabsorption, leading to low serum phosphate concentrations and an increased risk of kidney stones (nephrolithiasis) and bone demineralization (osteoporosis).

This condition is caused by heterozygous mutations in the SLC9A3R1 gene on chromosome 17q25. The mutation affects the function of the sodium-phosphate cotransporter, leading to impaired phosphate reabsorption in the kidneys.

Individuals with NPHLOP2 may experience a range of symptoms, including:

• Low serum phosphate concentrations
• Kidney stones (nephrolithiasis)
• Bone demineralization (osteoporosis)
• Increased risk of fractures

It's worth noting that NPHLOP2 is a rare condition and more research is needed to fully understand its causes and effects. However, early diagnosis and management can help alleviate symptoms and prevent complications.

References:

• [9] Hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2) is caused by heterozygous mutation in the SLC9A3R1 gene (604990) on chromosome 17q25.
• [10] Low serum phosphate concentrations due to a decrease in renal phosphate reabsorption have been reported in some patients with these conditions, suggesting that genetic factors leading to a decrease in renal phosphate reabsorption may contribute to the development of NPHLOP2.

Common Signs and Symptoms

Hypophosphatemic nephrolithiasis/osteoporosis is a rare genetic disorder characterized by phosphate loss in the proximal tubule, leading to various symptoms. The most common signs and symptoms include:

• Bone pain: A frequent complaint among affected individuals, often described as dull or sharp pains in the bones [6][7].
• Muscle weakness: Weakness and fatigue are common, particularly in the lower extremities [5][7].
• Pseudofractures: Also known as pseudorickets, these are areas of weakened bone that can appear on X-rays, often without any actual fractures [5].
• Rhabdomyolysis: A serious condition where muscle tissue breaks down, leading to muscle pain and weakness [4].
• Altered mental status: In severe cases, affected individuals may experience changes in their mental state, such as confusion or altered consciousness [4].

Additional Symptoms

Other symptoms associated with hypophosphatemic nephrolithiasis/osteoporosis include:

• Short stature: Affected children often have short stature due to rickets and impaired bone growth [6].
• Dental abnormalities: Some individuals may experience dental problems, such as tooth loss or early loss of baby teeth [8].
• Loss of teeth: In adults, affected individuals may lose their teeth prematurely [8].

References

[4] - Weakness, bone pain, rhabdomyolysis, and altered mental status are the most common presenting features. [5] - Bone pain, muscle weakness, and pseudofractures are the common presenting complaints, while no dental abnormalities are reported. They are more prone to ... [6] - X-linked hypophosphatemic rickets is characterized by short stature, radiographic evidence of rickets, and bone pain. Patients with this condition also may have ... [7] - In adults, chronic hypophosphatemia causes osteomalacia with musculoskeletal pain and weakness, especially involving the lower extremities and impaired ... [8] - Bone pain is common. Affected adults may experience loss of teeth. Some have a history of rickets during childhood, or baby teeth lost early ...

Diagnostic Tests for Hypophosphatemic Nephrolithiasis/Osteoporosis 2

Hypophosphatemic nephrolithiasis/osteoporosis 2 (NPHLOP2) is a rare genetic disorder characterized by abnormally decreased phosphate concentration in the blood. Diagnostic tests are essential to confirm this condition and rule out other possible causes.

Clinical Genetic Test A clinical genetic test, offered by PreventionGenetics as part of Exact Sciences, can be used to diagnose NPHLOP2 [1]. This test is specifically designed for patients with hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2) [3].

SLC34A1 Gene Test The SLC34A1 gene test is also available for diagnosing NPHLOP2. This test analyzes the SLC34A1 gene, which is associated with nephrolithiasis/hypophosphatemic osteoporosis type 1 and 2 [7].

Invitae Nephrolithiasis Panel The Invitae Nephrolithiasis Panel is another diagnostic tool that analyzes genes associated with nephrolithiasis, including those related to NPHLOP2 [8]. This panel can help identify the underlying genetic cause of the condition.

Genetic Testing for Diagnosis Genetic testing plays a crucial role in diagnosing NPHLOP2. A study published by D Prié et al. in 2002 found that genetic testing was essential for identifying patients with idiopathic hypophosphatemia associated with urolithiasis or bone demineralization [4].

References:

[1] Clinical Genetic Test offered by PreventionGenetics, part of Exact Sciences for conditions (1): Hypophosphatemic nephrolithiasis/osteoporosis 2; ...

[3] Candidates for this test are patients with hypophosphatemic nephrolithiasis/osteoporosis-2 (NPHLOP2). ... Note: acceptable specimen types are whole blood and DNA ...

[4] by D Prié · 2002 · Cited by 391 — Methods. We studied 20 patients with urolithiasis or bone demineralization and persistent idiopathic hypophosphatemia associated with a decrease in maximal ...

[7] SLC34A1 - nephrolithiasis / hypophosphatemic osteoporosis type 1. This test is available for the following conditions:.

[8] The Invitae Nephrolithiasis Panel analyzes genes that are associated with nephrolithiasis.

Treatment Options for Hypophosphatemic Nephrolithiasis/Osteoporosis

Hypophosphatemic nephrolithiasis/osteoporosis is a condition characterized by low phosphate levels in the blood, leading to kidney stones and osteoporosis. The conventional treatment for this condition involves multiple daily doses of oral phosphate salts and vitamin D metabolites or analogs as replacement therapy.

• Phosphate Supplementation: Long-term phosphorous supplementation can singularly cause remission and rapid correction of hypophosphatemia [4].
• Vitamin D Replacement: Vitamin D supplements are often used in conjunction with phosphate to help maintain normal calcium-phosphate metabolism.
• Bisphosphonates: Bisphosphonates, such as alendronate or risedronate, may be prescribed to prevent bone loss and reduce the risk of osteoporosis [7][8].
• Iron Therapy: Iron therapy has been shown to modify plasma FGF23 levels differently in autosomal dominant hypophosphatemic rickets and healthy humans [9].

The primary goals of pharmacotherapy for hypophosphatemia are to increase serum phosphate levels, reduce morbidity, and prevent complications. Supportive treatment with phosphate and low-dose vitamin D supplementation is also recommended.

References: [1] Suggest an ... Supportive treatment is with phosphate and low‐ dose vitamin D supplementation. [3] The conventional treatment consists of multiple daily doses of oral phosphate salts and vitamin D metabolites or analogs as replacement therapy, with a ... [4] Jul 9, 2020 — Currently, the only treatment for HHRH is long-term phosphorous supplementation which can singularly cause remission and rapid correction of ... [5] Mar 27, 2020 — Current treatment of hypophosphatemia mainly involves the supplementation of neutral phosphate. This can be achieved by two methods: oral ... [6] Mar 29, 2024 — The goals of pharmacotherapy are to increase serum phosphate levels, to reduce morbidity, and to prevent complications. [7] by K Sakhaee · 2011 · Cited by 204 — Bisphosphonates are popular and effective antiresorptive treatment drugs of osteoporosis. In genetic hypercalciuric stone-forming rats, treatment with ... [8] by K Sakhaee · 2011 · Cited by 204 — Bisphosphonates are popular and effective antiresorptive treatment drugs of osteoporosis. In genetic hypercalciuric stone-forming rats, ... [9] Imel EA, Peacock M, Gray AK, et al. Iron modifies plasma FGF23 differently in autosomal dominant hypophosphatemic rickets and healthy humans.

Differential Diagnosis of Hypophosphatemic Nephrolithiasis/Osteoporosis Type 2

Hypophosphatemic nephrolithiasis/osteoporosis type 2 (NPHLOP2) is a rare genetic disorder characterized by decreased renal phosphate reabsorption, leading to hypophosphatemia, nephrolithiasis, and osteoporosis. The differential diagnosis of NPHLOP2 includes other conditions that present with similar clinical features.

Conditions to Consider in the Differential Diagnosis:

• Hypophosphatemic rickets: A rare genetic disorder caused by mutations in the SLC34A1 gene, leading to decreased renal phosphate reabsorption and hypophosphatemia.
• Autosomal dominant hypophosphatemic rickets (ADHR): A rare genetic disorder caused by heterozygous point mutations at amino acid residues 176 or 179 in fibroblast growth factor 23 (FGF23), leading to decreased renal phosphate reabsorption and hypophosphatemia.
• Hereditary hypophosphatemic rickets with hypercalciuria: A rare genetic disorder caused by mutations in the SLC34A1 gene, leading to decreased renal phosphate reabsorption and increased urinary calcium excretion.

Key Features to Consider:

• Genetic testing: Genetic testing for mutations in the SLC34A1 gene can help confirm the diagnosis of NPHLOP2.
• Clinical presentation: Patients with NPHLOP2 typically present with hypophosphatemia, nephrolithiasis, and osteoporosis.
• Laboratory findings: Laboratory findings may include decreased renal phosphate reabsorption, increased urinary calcium excretion, and low bone mineral density.

References:

• [8] by MR Laurent · 2021 · Cited by 51 — Hypophosphatemic rickets has a wide differential diagnosis ... including hypophosphatemic nephrolithiasis/osteoporosis type 2.
• [11] This review serves as a practical guide to the evaluation of patients with a broad range of hypophosphatemic conditions, including NPHLOP2.

Note: The above information is based on the search results provided and may not be an exhaustive list of all possible differential diagnoses for hypophosphatemic nephrolithiasis/osteoporosis type 2.