vitamin D-dependent rickets type 2A

Vitamin D-Dependent Rickets Type 2A (VDDR2a)

Vitamin D-dependent rickets type 2A, also known as VDDR2a, is a rare genetic disorder caused by mutations in the gene encoding the vitamin D receptor (VDR) [5]. This condition leads to impaired vitamin D metabolism and results in softening and weakening of the bones (rickets) [1][6].

Characteristics

• Hypocalcemia: VDDR2a is characterized by low calcium levels in the blood, which can lead to muscle weakness, cramps, and spasms.
• Elevated calcitriol concentrations: The condition is also associated with elevated levels of 1,25-dihydroxyvitamin D (calcitriol), the active form of vitamin D [3].
• Alopecia: In many cases, VDDR2a manifests with hair loss (alopecia) [7].

Inheritance

VDDR2a 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 condition [8][9]. This means that carriers of the mutation are generally asymptomatic but can pass the mutated gene to their offspring.

Prevalence

Vitamin D-dependent rickets type 2A is a rare disorder, accounting for about 13% of total vitamin D-dependent rickets cases [4].

References: [1] Dec 1, 2017 — Vitamin D-dependent rickets is a disorder of bone development that leads to softening and weakening of the bones (rickets). [3] This form of rickets is characterized by hypocalcemia, elevated 1,25-dihydroxyvitamin D (calcitriol) concentrations and may also manifest with alopecia. [4] by M Thakur · 2019 · Cited by 13 — Vitamin D-dependent rickets is another form of bone disorder with rare oral manifestations, which is hereditary in origin, accounting for about 13% of total ... [5] by MA Levine · 2020 · Cited by 77 — Vitamin D-Dependent Rickets Type 2a (VDDR2a). VDDR2a (OMIM 277440) is due to biallelic loss-of-function mutations in the gene encoding the vitamin D receptor ( ... [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] A rare genetic, disorder of vitamin D metabolism characterized by hypocalcemia, severe rickets and in many cases alopecia. Traits & Categories for Vitamin D- ... [8] by K Demir · 2020 · Cited by 9 — Objective: Vitamin D–dependent rickets type 2A (VDDR2A) is a rare autosomal recessive disorder caused by mutations in the vitamin D receptor gene (VDR), leading ... [9] by NFB Rubaian · 2024 — Vitamin D-dependent rickets type II (VDDR2) is an inherited rare autosomal recessive disorder. This condition is also known as pseudovitamin D- ...

Vitamin D-dependent rickets type 2A (VDDR2A) is a rare genetic disorder that affects the body's ability to regulate calcium levels, leading to various signs and symptoms. Some of the common manifestations of VDDR2A include:

• Hypocalcemia: Low levels of calcium in the blood, which can cause muscle weakness, cramps, and spasms [4].
• Secondary hyperparathyroidism: An overactive parathyroid gland that produces excess parathyroid hormone, leading to increased calcium levels in the urine and decreased bone density [4].
• Low plasma concentrations of 25(OH)D: Reduced levels of 25-hydroxyvitamin D, a form of vitamin D that is essential for calcium absorption and bone health [4].

Additionally, VDDR2A may also manifest with other symptoms such as:

• Growth failure: Poor growth and development in children due to impaired bone mineralization [6].
• Limb bowing: Bowed legs or other skeletal deformities due to weakened bones [6].
• Joint pain: Pain and stiffness in the joints, particularly in the hands and feet [6].

It's essential to note that VDDR2A is a rare condition, and these symptoms may not be present in all cases. A proper diagnosis by a healthcare professional is necessary for accurate identification and treatment of this disorder.

References: [4] MA Levine · 2020 · Cited by 77 — [6] by AS Donmez · 2022 —

Diagnostic Testing for Vitamin D-Dependent Rickets Type 2A

Vitamin D-dependent rickets type 2A (VDDR2A) is a genetic disorder that affects the body's ability to activate vitamin D. Diagnostic testing plays a crucial role in confirming this condition.

• Serum 1,25(OH)2 Vitamin D Levels: Elevated or normal levels of serum 1,25(OH)2 vitamin D are indicative of VDDR2A [5][6].
• Genetic Testing: Genetic testing can confirm the presence of a defect in the vitamin D receptor gene, which is responsible for VDDR2A [7]. This type of testing can inform prognosis and clinical management.
• Clinical Examination and Radiographic Investigations: A thorough clinical examination and radiographic investigations are essential to diagnose VDDR2A. These may reveal signs such as widening of the epiphyseal plates, cupping and fraying of the epiphyseal end of the metaphysis, thinness of cortical bone, growth arrest lines, and bowing of the long bones of lower extremities [13][14].

Monitoring for Renal Calcification

Regular monitoring for renal calcification is also essential in patients with VDDR2A. A renal ultrasound examination should be performed every 1-2 years, or more frequently if there is evidence of calcification [4].

It's worth noting that delayed diagnosis can lead to severe skeletal

Vitamin D-dependent rickets type 2A (VDDR2A) is a rare genetic disorder characterized by impaired activation of vitamin D in the body, leading to softening and weakening of the bones. The cornerstone of treatment for VDDR2A is supplementation or pharmacological treatment with native or active vitamin D [7].

The combined administration of an active vitamin D metabolite and calcium salts is effective in treating vitamin D-dependent rickets, including type 2A [2][3]. This treatment approach helps to normalize calcium levels and promote bone mineralization.

In particular, the supplementation of calcitriol (1,25-dihydroxyvitamin D) has been shown to be effective in treating VDDR2A by overcoming the enzymatic block that impairs vitamin D activation [1].

It's worth noting that treatment with 1α-cholecalciferol is similarly effective as this metabolite also overcomes the enzymatic block, and due to its longer half-life, it may provide a more sustained therapeutic effect [1].

References: [1] by MA Levine · 2020 · Cited by 77 [2] by G Biasucci · 2024 · Cited by 4 [3] by G Biasucci · 2024 · Cited by 4 [7] by D Haffner · 2022 · Cited by 21

The differential diagnosis for vitamin D-dependent rickets type 2A (VDDR2A) includes other forms of rickets, such as hereditary and nutritional rickets, as well as atrichia with papular lesions (APL) and hypocalcemic vitamin D-dependent rickets.

Other Forms of Rickets:

• Hereditary rickets: This is a genetic disorder that affects the development of bones, leading to softening and weakening of the bones.
• Nutritional rickets: This type of rickets occurs when there is a deficiency in vitamin D or calcium in the diet, leading to softening and weakening of the bones.

Atrichia with Papular Lesions (APL):

• APL is a rare genetic disorder characterized by hair loss and skin lesions.
• It can be associated with hypocalcemia and vitamin D-dependent rickets type 2A.

Hypocalcemic Vitamin D-Dependent Rickets:

• This is another form of vitamin D-dependent rickets that is caused by mutations in the vitamin D receptor gene (VDR).
• It is characterized by low calcium levels in the blood and can be associated with VDDR2A.

It's worth noting that a definitive diagnosis of VDDR2A requires genetic testing to confirm the presence of mutations in the VDR gene. [7][8]

References: [7] - The differential diagnosis includes other forms of rickets (hereditary and nutritional) and atrichia with papular lesions (APL) and hypocalcemic vitamin D-dependent rickets. [8] - The genetic diagnosis of autosomal recessive vitamin D-dependent rickets type 2A (VDDR2A) is confirmed.