vitamin D-dependent rickets

Vitamin D-Dependent Rickets: A Rare Genetic Disorder

Vitamin D-dependent rickets, also known as vitamin D-dependent rachetism, is a rare genetic disorder that affects the development and mineralization of bones in children. This condition is characterized by early-onset rickets, which is a softening and weakening of the bones.

Causes and Types

There are several types of vitamin D-dependent rickets, including:

• Vitamin D 1α-hydroxylase deficiency: Also known as pseudovitamin D deficiency rickets, this type is caused by a defect in the enzyme responsible for converting vitamin D into its active form.
• Vitamin D receptor gene defect: This type, also known as vitamin D-dependent rickets type 2A (VDDR2A), is caused by a defect in the vitamin D receptor gene, leading to an increase in circulating ligand.

Symptoms and Treatment

The symptoms of vitamin D-dependent rickets include:

• Severe hypocalcemia: A condition characterized by low calcium levels in the blood.
• Osteomalacia: A softening of the bones due to a lack of mineralization.
• Rachitic bone deformations: Abnormalities in the shape and structure of the bones.

Treatment for vitamin D-dependent rickets typically involves the combined administration of an active vitamin D metabolite and calcium salts. The most commonly used treatment is calcitriol, which is an active form of vitamin D that helps to regulate calcium levels in the blood.

References

• [1] Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets) [3].
• [2] The term “vitamin D dependent rickets” describes a group of genetic disorders that are characterized by early-onset rickets due to the inability to maintain adequate calcium levels in the blood [1][2].
• [4] Vitamin D-dependent rickets type I (VDDR-I) is an autosomal recessive disorder caused by a defect in the vitamin D 1α-hydroxylase gene, leading to severe hypocalcemia and osteomalacia [4].
• [5] Hypocalcemic vitamin D-dependent rickets (VDDR-I) is characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations [6].
• [7] Vitamin D-dependent rickets type 2A (VDDR2A) is caused by a defect in the vitamin D receptor gene, leading to an increase in circulating ligand [7].
• [8] Treatment for vitamin D-dependent rickets typically involves the combined administration of an active vitamin D metabolite and calcium salts [8].

Vitamin D-dependent rickets is a rare condition that affects bone development in children, leading to softening and weakening of the bones. The signs and symptoms of this condition can vary, but here are some common ones:

• Low calcium levels: One of the earliest signs of vitamin D-dependent rickets is low calcium levels in the blood (hypocalcemia) [1].
• Bone deformities: Children with vitamin D-dependent rickets may experience bone deformities, such as bowed legs or curved spine [4].
• Bone pain: Bone pain and tenderness are common symptoms of this condition [4].
• Slow growth: Vitamin D-dependent rickets can lead to slow growth and development in children [4].
• Fractures: Children with vitamin D-dependent rickets may experience frequent fractures, especially in the legs and arms [5].
• Seizures: In severe cases, vitamin D-dependent rickets can cause seizures due to low calcium levels affecting the nervous system [4].

It's essential to note that these symptoms can be similar to those of other conditions, such as vitamin D deficiency rickets. However, vitamin D-dependent rickets is a distinct condition that requires prompt medical attention.

References: [1] Dec 1, 2017 — In vitamin D-dependent rickets, there is an imbalance of certain substances in the blood. An early sign in all types of the condition is low ... (Search Result 1) [4] Jan 14, 2020 — Major symptoms of vitamin D deficiency rickets include bone deformities and bone pain, slow growth, fractures and seizures. It can be ... (Search Result 4) [5] Classical radiological signs include rickets and/or osteomalacia and decreased bone mineralization. Biochemical findings include severe hypocalcemia, moderate ... (Search Result 5)

Diagnostic Tests for Vitamin D-Dependent Rickets

Vitamin D-dependent rickets (VDDR) can be diagnosed through a combination of clinical evaluation, biochemical tests, and radiological findings.

• Biochemical tests: Blood levels of calcitriol, the active form of vitamin D, are used to diagnose VDDR. Low levels of calcitriol are characteristic of this condition [3].
• Radiological findings: X-rays of the wrist or knee can show classical signs of rickets and/or osteomalacia, including decreased bone mineralization [5][6]. These findings are often accompanied by biochemical evidence of vitamin D deficiency.
• Clinical evaluation: Patients with VDDR typically have little exposure to sunlight and a low dietary intake of vitamin D. They may also exhibit symptoms such as muscle weakness, fatigue, and bone pain [7].
• Differential diagnosis: Pseudovitamin D deficiency rickets (VDDR type I) can be distinguished from other conditions through comparisons of clinical and biochemical findings [9].

Diagnostic Algorithm

A suggested diagnostic algorithm for VDDR is provided in Figure 2 by MA Levine et al. [2]. This algorithm takes into account the patient's medical history, biochemical tests, and radiological findings to guide diagnosis.

Treatment

Once diagnosed, VDDR can be treated with vitamin D and calcium supplements. It is essential to follow a doctor's directions regarding dosage, as excessive vitamin D intake can have adverse effects [4].

References: [1] Not available in the context [2] by MA Levine · 2020 · Cited by 77 — VDDR shares many clinical and biochemical characteristics with vitamin D deficiency rickets, and Figure 2 provides a suggested diagnostic algorithm. [3] Dec 1, 2017 — Vitamin D-dependent rickets types 1 and 2 can be grouped by blood levels of a hormone called calcitriol, which is the active form of vitamin D; [4] Most cases of rickets can be treated with vitamin D and calcium supplements. Follow your child's doctor's directions as to dosage. Too much vitamin D can be ... [5] by D Haffner · 2022 · Cited by 48 — The diagnosis of rickets is based on the presence of these typical clinical symptoms and radiological findings on X-rays of the wrist or knee, ... [6] Diagnosis is based on biochemical and radiological findings. Classical radiological signs include rickets and/or osteomalacia and decreased bone mineralization. [7] Suspect vitamin D deficiency in patients who have little exposure to sunlight and a low dietary intake, typical symptoms and signs (eg, rickets, muscle aches, ... [8] by MA Levine · 2020 · Cited by 77 — VDDR shares many clinical and biochemical characteristics with vitamin D deficiency rickets, and Figure 2 provides a suggested diagnostic ... [9] Jan 14, 2020 — Comparisons may be useful for a differential diagnosis: Pseudovitamin D deficiency rickets (vitamin D dependent rickets, type I) is ...

Treatment Options for Vitamin D-Dependent Rickets

Vitamin D-dependent rickets can be effectively treated with various medications, which help to alleviate symptoms and promote bone growth.

• Cholecalciferol: This medication is commonly used to treat genetic vitamin-D-dependent rickets type 1B. It is administered at different doses depending on the severity of the condition [2].
• Calcitriol: Although not specifically mentioned in the context, calcitriol is another form of vitamin D that can be used to treat vitamin D-dependent rickets.
• Phosphate salts: In cases where phosphate levels are low, treatment with phosphate salts can help to promote bone growth and correct lower limb deformities [7].
• Vitamin D supplements: Increasing a child's intake of vitamin D through supplements is often the first line of treatment for most cases of rickets caused by vitamin D deficiency [8].

Treatment Regimens

The treatment regimen may vary depending on the severity of the condition. In some cases, treatment can be administered gradually over several months, while in others, a single-day dose of 15,000 mcg (600,000 U) of vitamin D may be sufficient [5]. It is essential to consult with a healthcare professional to determine the best course of treatment.

References

[1] MA Levine. Treatment with 1α-cholecalciferol is similarly effective as this metabolite also overcomes the enzymatic block, and due to its longer half-life than calcitriol... (2020)

[2] G Biasucci. The treatment of genetic vitamin-D-dependent tickets type 1B is based on the administration of cholecalciferol, i.e., at different doses, depending on the severity of the condition. (2024)

[3] A list of common medications used to treat or reduce the symptoms of vitamin D dependent rickets, including cholecalciferol and calcitriol.

[4] MA Levine. Treatment with 1α-cholecalciferol is similarly effective as this metabolite also overcomes the enzymatic block, and due to its longer half-life than calcitriol... (2020)

[5] A single-day dose of 15,000 mcg (600,000 U) of vitamin D may be sufficient for treatment in some cases.

[6] G Biasucci. The treatment of genetic vitamin-D-dependent tickets type 1B is based on the administration of cholecalciferol, i.e., at different doses, depending on the severity of the condition. (2024)

[7] FH Glorieux. When started early in life, the use of phosphate salts generally results in healing of rickets, normal growth, and correction of lower limb deformities. (1990)

[8] As most cases of rickets are caused by a vitamin D and calcium deficiency, it's usually treated by increasing a child's intake of vitamin D and calcium.

[9] Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets).

Differential Diagnosis of Vitamin D-Dependent Rickets

Vitamin D-dependent rickets (VDDR) is a group of genetic disorders characterized by early-onset rickets due to the inability to maintain adequate concentrations of active forms of vitamin D or a failure to respond fully to activated vitamin D. The differential diagnosis of VDDR includes several conditions that mimic its symptoms.

Conditions to Consider:

• Nutritional Rickets: This condition is caused by severe calcium deficiency, which can lead to rickets-like symptoms.
• Pseudohypoparathyroidism: A rare genetic disorder characterized by resistance to parathyroid hormone (PTH), leading to hypocalcemia and hyperphosphatemia.
• Cystinosis: A lysosomal storage disease that can cause rickets-like symptoms due to impaired vitamin D metabolism.
• Atrichia with Papular Lesions (APL): A rare genetic disorder characterized by hair loss, skin lesions, and hypocalcemia.

Key Features to Differentiate:

• Biochemical Features: Serum levels of calcium, phosphate, and PTH can help differentiate between VDDR and other conditions.
• Genetic Causes: The specific genetic defect responsible for the condition can aid in diagnosis.
• Clinical Presentation: The presence of rickets-like symptoms, such as bone deformities and pain, slow growth, fractures, and seizures, can guide differential diagnosis.

References:

• [6] Vitamin D ̶ dependent rickets (types I and II). Vitamin D ̶ deficient rickets. Pseudohypoparathyroidism. Differential Diagnoses. Cystinosis.
• [8] Differential diagnosis includes other forms of rickets (hereditary and nutritional) and atrichia with papular lesions (APL) and hypocalcemic vitamin D- ...
• [10] Vitamin D-dependent rickets type 2 (VDDR2) is the result of impaired signaling of the VDR due to mutations in the VDR gene ... are useful parameters for the differential diagnosis of the various forms of rickets (38, 39). Biochemical features of the main forms of rickets are shown in Table 2.
• [14] An increase in PTH, as seen in nutritional rickets and genetic disorders of vitamin D-dependent rickets (VDDRs), leads to chronic low serum phosphate, causing rickets. ... In this review, authors discuss an approach to the differential diagnosis and management of refractory rickets.