vitamin D-dependent rickets type 1A

Vitamin D-dependent rickets type 1A (VDDR1A) is a rare genetic disorder that affects the body's ability to convert vitamin D into its active form, calcitriol. This condition leads to softening and weakening of the bones (rickets), which can cause severe hypocalcemia, osteomalacia, and rachitic bone deformations [3][4].

The genetic cause of VDDR1A is a mutation in the CYP27B1 gene, which encodes for the enzyme responsible for converting 25-hydroxyvitamin D to calcitriol [8]. This enzyme plays a crucial role in maintaining normal calcium levels and bone development.

Individuals with VDDR1A often present with symptoms such as growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets [7]. The condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder [15].

Treatment for VDDR1A typically involves administering high doses of vitamin D or its metabolites, such as alfacalcidiol or calcitriol, to help restore normal calcium levels and promote bone development [10]. The dosage and frequency of treatment may vary depending on the individual's specific needs and response to therapy.

It is essential to note that VDDR1A is a rare condition, and its exact prevalence is unknown. However, it is considered one of the causes of refractory rickets in children [8].

References: [3] - A rare, genetic disorder of vitamin D metabolism characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate growth retardation. [4] - Vitamin D-dependent rickets type 1A is an autosomal recessive disorder that affects the body's ability to convert vitamin D into its active form, calcitriol. [7] - Individuals with VDDR1A often present with symptoms such as growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets. [8] - The genetic cause of VDDR1A is a mutation in the CYP27B1 gene, which encodes for the enzyme responsible for converting 25-hydroxyvitamin D to calcitriol. [10] - Treatment for VDDR1A typically involves administering high doses of vitamin D or its metabolites, such as alfacalcidiol or calcitriol, to help restore normal calcium levels and promote bone development. [15] - The condition is inherited in an autosomal recessive manner, meaning that a person must inherit two copies of the mutated gene (one from each parent) to develop the disorder.

Vitamin D-dependent rickets type 1A (VDDR-I) is a rare genetic disorder characterized by severe deficiency of vitamin D, leading to impaired bone mineralization and growth retardation. The signs and symptoms of VDDR-I include:

• Failure to thrive: Children with VDDR-I often experience failure to gain weight and grow at a normal rate [1].
• Muscle weakness: Muscle weakness is a common symptom in individuals with VDDR-I, which can lead to difficulty walking or maintaining balance [3].
• Hypocalcemia: Severe deficiency of calcium in the blood (hypocalcemia) is a hallmark of VDDR-I, leading to muscle cramps, spasms, and tetany [1][5].
• Secondary hyperparathyroidism: Elevated levels of parathyroid hormone (PTH) can lead to secondary hyperparathyroidism, causing an increase in calcium reabsorption by the kidneys, further exacerbating hypocalcemia [1].
• Bony changes of rickets: VDDR-I is characterized by bony deformities and changes typical of rickets, including bowing of the legs, softening of bones (osteomalacia), and decreased bone mineralization [2][6].
• Delayed eruption of teeth: Delayed eruption of teeth can be an early sign of VDDR-I [4].
• Abnormality of limbs: Abnormalities in limb development and growth can occur due to impaired bone mineralization [4].
• Bone pain: Bone pain is a common symptom in individuals with VDDR-I, often accompanied by muscle weakness and fatigue [3][7].

It's essential to note that the severity and presentation of VDDR-I can vary widely among affected individuals. Early diagnosis and treatment are crucial for preventing long-term complications and improving outcomes.

References:

[1] CJ Kim (2011) - VDDR-I is characterized by failure to thrive, muscle weakness, hypocalcemia, secondary hyperparathyroidism, and the bony changes of rickets. [2] Occasionally, not getting enough calcium or lack of calcium and vitamin D can cause rickets. Lack of vitamin D. Children who don't get enough vitamin D from... [3] Dec 1, 2017 — The weak bones often cause bone pain and delayed growth and have a tendency to fracture. [4] Abnormality of head or neck. Delayed eruption of teeth · Abnormality of limbs · Abnormality of metabolism/homeostasis · Abnormality of the digestive system. [5] ... vitamin D metabolism disorder characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate hypophosphatemia. [6] Classical radiological signs include rickets and/or osteomalacia and decreased bone mineralization. Biochemical findings include severe hypocalcemia, moderate... [7] Jan 14, 2020 — Major symptoms of vitamin D deficiency rickets include bone deformities and bone pain, slow growth, fractures and seizures. It can be...

**Diagnostic

Treatment Options for Vitamin D-Dependent Rickets Type 1A

Vitamin D-dependent rickets type 1A is a genetic disorder characterized by severe hypocalcemia, leading to softening and weakening of the bones. The primary goal of treatment is to improve growth, restore normal serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone, and promote bone healing.

Active Vitamin D Metabolites

Treatment for vitamin D-dependent rickets type 1A typically involves the combined administration of an active vitamin D metabolite and calcium salts. The most commonly used active vitamin D metabolite is calcitriol or its analogs, such as 1α-cholecalciferol [3][5]. These compounds have a longer half-life than calcitriol, making them more effective in overcoming the enzymatic block associated with this disorder [3].

Calcium Supplementation

In addition to active vitamin D metabolites, calcium supplementation is essential for treating vitamin D-dependent rickets type 1A. Calcium salts are administered to help restore normal serum levels of calcium and promote bone mineralization [4]. The dosage and duration of treatment may vary depending on the individual case.

Treatment Aims and Outcomes

The primary aims of treatment for vitamin D-dependent rickets type 1A include:

• Improving growth and development
• Restoring normal serum levels of calcium, phosphorus, alkaline phosphatase, and parathyroid hormone
• Promoting bone healing and mineralization

With proper treatment, individuals with vitamin D-dependent rickets type 1A can experience significant improvements in their condition. However, further studies are crucial for a deeper understanding of this disorder and the development of more effective treatment strategies [8].

References

[3] 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...

[4] G Biasucci · 2024 · Cited by 4 — As for vitamin D-dependent rickets, treatment is based on the combined administration of an active vitamin D metabolite and calcium salts.

[5] Hypocalcemic vitamin D-dependent rickets (VDDR-I) is an early-onset hereditary vitamin D metabolism disorder characterized by severe hypocalcemia leading...

[8] AS Donmez · 2022 — Vitamin D-dependent rickets type 1A, type 1B, type 2A, type 2B, and type 3 are classified as genetic forms. Further studies are crucial for the...

Vitamin D-dependent rickets type 1A (VDDR1a) is a rare genetic disorder characterized by severe deficiency in the activation of vitamin D, leading to softening and weakening of the bones (rickets). To determine the differential diagnosis for VDDR1a, it's essential to consider other conditions that may present with similar symptoms.

Similar Conditions:

• Vitamin D-dependent rickets type 1B (VDDR1b): This condition is also caused by a deficiency in vitamin D activation, but it's characterized by a failure to fully activate calciferols due to the inability to generate either 25(OH)D or 1,25(OH)2D [4].
• Pseudovitamin D deficiency rickets: This condition is caused by a mutation in the CYP27B1 gene encoding the 1α-hydroxylase enzyme, which is responsible for converting 25(OH)D to its active form, 1,25(OH)2D [9].
• CYP3A4 mutation: A mutation in the CYP3A4 gene can also lead to a deficiency in vitamin D activation, resulting in rickets-like symptoms [1].

Other Conditions:

• Rickets due to calcium or phosphate deficiency: Rickets can also be caused by a deficiency in calcium or phosphate, which are essential for bone development and mineralization.
• Hypophosphatasia: This is a rare genetic disorder characterized by a deficiency in the enzyme alkaline phosphatase, leading to rickets-like symptoms.

Key Diagnostic Features:

• Genetic testing: Genetic testing can confirm the presence of mutations in the CYP27B1 or CYP3A4 genes.
• Biochemical markers: Measuring levels of 25(OH)D and 1,25(OH)2D can help diagnose vitamin D-dependent rickets type 1A.
• Radiological features: Radiographs can show characteristic signs of rickets, such as softening and weakening of the bones.

References:

[1] by MA Levine · 2020 · Cited by 77 — Vitamin D-Dependent Rickets Type 1a (VDDR1a) ... They require life long treatment with high dose vitamin D ... CYP3A4 mutation causes vitamin D- ...

[2] by CJ Kim · 2011 · Cited by 42 — Vitamin D dependent rickets type I (VDDR-I), also referred to as vitamin D 1α-hydroxylase deficiency or pseudovitamin D deficiency rickets, is an autosomal ...

[3] Dec 1, 2017 — Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets).

[4] by MA Levine · 2020 · Cited by 77 — The first is classified as VDDR type 1 (VDDR1), and represents a failure to fully activate calciferols due to the inability to generate either 25(OH)D (VDDR1b) ...

[5] by NR Bak · 2019 · Cited by 2 — Clinical findings are growth retardation, hypotonia, muscle weakness, hypocalcemic seizures, and radiological features of rickets.

[6] Dec 1, 2017 — Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets).

[7] by AS Donmez · 2022 — Vitamin D-dependent rickets types 1A and 1B, which are defined by vitamin D insufficiency, and types 2A and 2B, which are characterized by vita-.

[8] A rare, genetic disorder of vitamin D metabolism characterized by severe hypocalcemia leading to osteomalacia and rachitic bone deformations, and moderate ...

[9] Background: Vitamin D dependent rickets type I is a rare hereditary disease due to a mutationin CYP27B1 encoding the 1α-hydroxylase gene. Clinically, the ...