vitamin D-dependent rickets type 1B

Vitamin D-dependent rickets type 1B (VDDR1B) is a rare genetic disorder caused by a defect in vitamin D 25-hydroxylation [4]. This condition leads to impaired activation of vitamin D, resulting in softening and weakening of the bones (rickets) due to inadequate calcium-phosphate product for bone mineralization [13].

The symptoms of VDDR1B include reduced serum concentrations of 25-hydroxyvitamin D, hypophosphatemia, hypocalcemia with secondary hyperparathyroidism, and osteomalacia or rachitic bone deformations [11]. This condition is characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate to severe elevation of serum alkaline phosphatase levels [15].

VDDR1B is caused by mutations in the gene responsible for vitamin D 25-hydroxylase activity, which is essential for converting vitamin D into its active form [4]. This genetic defect leads to a failure in activating vitamin D, resulting in the symptoms associated with VDDR1B.

It's worth noting that VDDR1B is one of four rare genetic errors of vitamin D metabolism that can cause rickets, and it is most common among these conditions [14].

Vitamin D-dependent rickets type 1B (VDDR1B) is a rare genetic disorder characterized by severe vitamin D deficiency, leading to various signs and symptoms.

Clinical Features:

• Enlargement of the ankles
• Enlargement of the wrists
• Fibular bowing
• Tibial bowing
• Decreased circulating calcifediol concentration

These clinical features are indicative of a severe vitamin D deficiency, which can lead to rickets and osteomalacia in affected individuals.

Common Symptoms:

• Abnormality of head or neck
• Delayed eruption of teeth
• Abnormality of limbs
• Abnormality of metabolism/homeostasis
• Abnormality of the digestive system

These symptoms are often associated with vitamin D deficiency rickets and can be seen in individuals with VDDR1B.

Classical Radiological Signs:

• Rickets and/or osteomalacia
• Decreased bone mineralization

Biochemical findings, including severe hypocalcemia and moderate hypophosphatemia, are also characteristic of this condition.

Major Symptoms:

• Bone deformities and bone pain
• Slow growth
• Fractures
• Seizures

These symptoms can be seen in individuals with vitamin D deficiency rickets, including those with VDDR1B.

According to [6], VDDR1B is a rare genetic disorder characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate hypophosphatemia. This condition is often associated with little exposure to sunlight and low dietary intake of vitamin D.

References: [1] - Clinical features indicative of vitamin D deficiency [2] - Symptoms associated with vitamin D deficiency rickets [3] - Classical radiological signs of vitamin D-dependent rickets type 1B [4] - Biochemical findings in VDDR1B [5] - Major symptoms of vitamin D deficiency rickets [6] - Definition and characteristics of VDDR1B

Vitamin D-dependent rickets type 1B (VDDR1B) can be diagnosed through various tests that measure the levels of certain hormones and nutrients in the blood.

• Serum calcium and PTH levels should be maintained in the mid-normal range [1].
• Blood tests can also measure the levels of calcitriol, which is the active form of vitamin D [3].
• Genetic testing for CYP2R1 mutations can also be performed to confirm a diagnosis of VDDR1B [2].

It's worth noting that biochemical analyses may reveal signs of vitamin D deficiency and nutritional rickets, such as lower limb radiography images showing bone softening and weakening [6].

In terms of specific diagnostic tests, serum levels of 25(OH)D, 1,25-dihydroxyvitamin D, calcium, and phosphate can be measured to confirm a diagnosis of VDDR1B. For example, type I hereditary vitamin D–dependent rickets results in normal serum 25(OH)D, low serum 1,25-dihydroxyvitamin D and calcium, and normal or low serum phosphate [9].

References: [1] MA Levine · 2020 · Cited by 76 [2] Clinical resource with information about Vitamin D hydroxylation-deficient rickets type 1B and its clinical features, CYP2R1, available genetic tests from ... [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; ... [6] by A Molin · 2017 · Cited by 78 — Biochemical analyses were suggestive of vitamin D deficiency and nutritional rickets, as revealed in the lower limb radiography images (Fig. 2). [9] Type I hereditary vitamin D–dependent rickets results in normal serum 25(OH)D, low serum 1,25-dihydroxyvitamin D and calcium, and normal or low serum phosphate.

Treatment Options for Vitamin D-Dependent Rickets Type 1B

Vitamin D-dependent rickets type 1B (VDDR1B) is a rare genetic disorder that affects the body's ability to convert vitamin D into its active form, leading to softening and weakening of the bones. The treatment of VDDR1B focuses on correcting the underlying metabolic defect and managing symptoms.

Active Vitamin D Metabolites

The primary treatment for VDDR1B involves administering an active vitamin D metabolite, such as calcitriol or 1α-cholecalciferol, in combination with calcium salts. This approach helps to restore normal serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone [7].

Calcium Supplementation

In addition to active vitamin D metabolites, patients with VDDR1B often require calcium supplementation to maintain adequate bone mineralization and prevent hypocalcemia. The dosage of calcium salts is typically tailored to the individual patient's needs [4].

Long-term Treatment

Unlike some other forms of vitamin D-dependent rickets, treatment for VDDR1B must be continued for life. This ensures that patients receive consistent levels of active vitamin D metabolites and calcium salts, helping to maintain normal bone mineralization and prevent complications [2].

References:

• [4] G Biasucci (2024) - Treatment of genetic vitamin-D-dependent rickets
• [7] by MA Levine · 2020 · Cited by 77 — Treatment with 1α-cholecalciferol is similarly effective as this metabolite also overcomes the enzymatic block, and due to its longer half-life than calcitriol, ...
• [2] by G Biasucci · 2024 · Cited by 4 — Treatment of genetic vitamin-D-dependent rickets must be continued for life, with patient tailored doses.

The differential diagnosis for vitamin D-dependent rickets type 1B (VDDR1B) includes nutritional vitamin D deficiency, vitamin D resistant rickets, and bone dysplasia.

Nutritional vitamin D deficiency is a condition where the body does not get enough vitamin D from food or sunlight, leading to impaired bone mineralization. Vitamin D resistant rickets, on the other hand, is a rare genetic disorder that affects the body's ability to convert vitamin D into its active form, calcitriol.

Bone dysplasia refers to a group of disorders that affect the development and growth of bones. These conditions can lead to abnormalities in bone shape, size, and density, which may be similar to those seen in VDDR1B.

It is essential to confirm the diagnosis through DNA analysis to rule out these differential diagnoses. [5]

VDDR1B is caused by a defect in vitamin D 25-hydroxylation, making it crucial to distinguish this condition from other bone disorders that may present with similar symptoms. [4]