obsolete familial hypophosphatemia

Obsolete Familial Hypophosphatemia: A Rare Genetic Disorder

Obsolete familial hypophosphatemia, also known as familial hypophosphatemic rickets, is a rare genetic disorder characterized by an inherited defect in phosphate reabsorption and vitamin D metabolism in the kidneys [3]. This condition leads to a range of symptoms, including:

• Hypophosphatemia: A deficiency of phosphate ions in the blood [7][8]
• Rickets: Softening of bones in children due to defective mineralization [4]
• Osteomalacia: Softening of bones in adults due to defective mineralization [3]

The disorder is caused by mutations in genes that regulate phosphate and vitamin D metabolism, leading to impaired renal reabsorption of phosphate and altered vitamin D metabolism [10]. This results in the excessive excretion of phosphate in the urine, contributing to the development of hypophosphatemia and rickets.

Clinical Manifestations

The clinical manifestations of obsolete familial hypophosphatemia can be attributed to two metabolic consequences of cellular phosphate depletion:

• Reduction of ATP: The reduction of adenosine triphosphate (ATP) levels in cells, leading to impaired energy metabolism [9]
• Mineral defects in bones: Impaired mineralization of bones, resulting in rickets and osteomalacia [3]

References

[1] Not Available [2] Not Available [3] A hereditary disorder characterized by HYPOPHOSPHATEMIA; RICKETS; OSTEOMALACIA; renal defects in phosphate reabsorption and vitamin D metabolism; [4] by R Chanchlani · 2020 · Cited by 105 — Rickets is a common bone disease worldwide that is associated with disturbances in calcium and phosphate homeostasis and can lead to short stature and joint ... [5] familial hypophosphatemia. Human disease ... obsolete familial hypophosphatemia. [6] Familial Hypophosphatemic Rickets/enzymology · Familial Hypophosphatemic Rickets/genetics · [OBSOLETE] Familial Hypophosphatemic Rickets/radionuclide imaging [7] Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is ... [8] Hypophosphatemic rickets are associated with renal excretion of phosphate, hypophosphatemia, and mineral defects in bones. The familial type of the disease is ... [9] The clinical manifestations of hypophosphatemia can be attributed to two metabolic consequences of cellular phosphate depletion: (1) the reduction of ATP ... [10] by V Tejwani · 2013 · Cited by 50 — Rare forms of FGF23 gain-of-function [112] and loss-of-function [113] mutations can cause familial forms of hyper- or hypophosphatemia, vitamin D alterations ...

Common Signs and Symptoms

X-linked hypophosphatemia (XLH) is a rare, hereditary, progressive musculoskeletal disease that often causes pain and short stature, as well as decreased bone mineralization. The main clinical symptoms in children are:

• Abnormal gait
• Lower limb deformity
• Decreased growth velocity
• Dental abscesses

In adults, the most notable side effects include: * Bone pain * Muscle weakness * Pseudo fractures * Short stature * Frontal bossing * Abscessed teeth * Enthesopathy (inflammation of tendons and ligaments) * Osteoarthritis

Additional Symptoms

Other symptoms associated with XLH include:

• Lower limb deformities
• Clinical and radiological signs of osteomalacia
• Insufficiency fractures
• Dental problems, such as tooth decay and gum disease
• Muscle weakness and wasting
• Joint pain and stiffness

Complications

If left untreated or undertreated, XLH can lead to complications such as:

• Hypercalcemia (elevated calcium levels)
• Nephrocalcinosis (kidney stones)
• Nephrolithiasis (kidney damage)
• Impaired renal function
• Secondary hyperparathyroidism (overactive parathyroid glands)

References

1. Haffner, D., et al. "X-linked hypophosphatemia: a review of the literature." [1]
2. Dahir, K., et al. "X-linked hypophosphatemia: a rare cause of short stature and musculoskeletal pain." [2]
3. Hamdy, N. A., et al. "Clinical manifestations in adults with X-linked hypophosphatemia." [3]

Note: The references provided are based on the search results and may not be an exhaustive list of all relevant studies.

Based on the provided context, it appears that there are various diagnostic tests for familial hypophosphatemia (FH), including:

• Biochemical testing of blood and urine to reveal a low serum phosphate level in the setting of normal serum calcium and 25-hydroxyvitamin D levels [1].
• Radiology, biochemistry, and genetic investigations as part of a detailed medical examination, including family history, auxology, and musculoskeletal examination [2].
• Genetic testing to confirm the diagnosis of X-linked hypophosphatemia (XLH) and other forms of FGF23-dependent hypophosphatemia [6][7].

Additionally, molecular genetic testing can be used to confirm the diagnosis of XLH and provide information on the inheritance pattern of the disorder [8]. It's also worth noting that differential diagnosis includes autosomal dominant and autosomal recessive hypophosphatemic rickets, which should be considered when evaluating patients with suspected FH [7].

In terms of obsolete diagnostic tests for familial hypophosphatemia, it's not clear what specific tests are being referred to. However, it's possible that older tests such as:

• Serum phosphate level measurements alone may have been used in the past to diagnose FH, but this would not be sufficient on its own due to the complexity of the disorder [11].
• Other outdated tests or criteria for diagnosing FH may have been used prior to the development of more modern and comprehensive diagnostic approaches.

It's worth noting that the diagnosis of FH is typically confirmed through a combination of clinical, radiographic, biochemical, and genetic features, as well as molecular genetic testing.

Based on the provided context, it appears that there are limited treatment options available for familial hypophosphatemia (FH), a condition characterized by excess kidney losses of phosphate.

Current Treatment Options

• Oral phosphorous supplementation is a common treatment approach for FH. According to search result [8], medical therapy should be initiated once the diagnosis of XLH (a related condition) is made, consisting of oral phosphorous (starting at 20-60 mg/kg body weight).
• Neutral phosphate solution or tablets are also used to treat hypophosphatemic rickets, a condition closely related to FH. Search result [6] mentions that phosphate supplementation lowers ionized calcium concentrations and can help alleviate symptoms.

Emerging Therapies

• Burosumab, a drug approved by the FDA in 2018 (search result [4]), targets FGF23 and has shown promise in treating X-linked hypophosphatemia (XLH), a related condition. Search results [5] and [9] highlight the potential of burosumab therapy not only for XLH but also for other conditions with FGF23 dysregulation.
• However, it's essential to note that there is limited information available on the specific treatment of familial hypophosphatemia (FH) using burosumab or other emerging therapies.

Important Considerations

• Treatment should address the underlying cause when possible, removing causative drugs or addressing dietary deficiencies. Search result [14] emphasizes the importance of obtaining proper biochemical testing to identify renal or nonrenal hypophosphatemia before initiating treatment.
• It's also crucial to note that treatment goals and options may vary depending on individual patient needs and circumstances.

In summary, while there are some established treatment options for familial hypophosphatemia (FH), such as oral phosphorous supplementation, emerging therapies like burosumab hold promise in treating related conditions. However, more research is needed to determine the efficacy of these treatments specifically for FH.

Based on the provided context, it appears that differential diagnosis for familial hypophosphatemia may involve several conditions that share similar symptoms.

Similarities with other disorders

• Rickets caused by vitamin D deficiency can have overlapping symptoms with familial hypophosphatemia, including reduced availability of dietary calcium [1].
• Hereditary hypophosphatemic rickets with hypocalciuria is another condition that may be considered in the differential diagnosis, as it also involves impaired phosphate reabsorption in the kidneys [2].

Other conditions to consider

• Renal tubular acidosis can present with similar symptoms, including electrolyte imbalances and kidney dysfunction [3].
• Fanconi syndrome (types I and II) is a genetic disorder that affects the kidneys' ability to reabsorb glucose, amino acids, and phosphate, leading to similar symptoms as familial hypophosphatemia [4].

Key differences

While these conditions share some similarities with familial hypophosphatemia, they have distinct underlying causes and manifestations. For instance:

• Rickets caused by vitamin D deficiency is typically associated with a deficiency in calcium absorption, whereas familial hypophosphatemia involves impaired phosphate reabsorption.
• Hereditary hypophosphatemic rickets with hypocalciuria has a more severe impact on phosphate levels, often leading to significant skeletal deformities [5].

Important considerations

When considering differential diagnoses for familial hypophosphatemia, it is essential to take into account the patient's medical history, family history, and examination results. A thorough assessment of renal tubular phosphate handling can help identify the underlying cause of the condition [13].

References:

[1] Context result 2 [2] Context result 6 [3] Context result 3 [4] Context result 2 [5] Context result 8