autosomal recessive osteopetrosis 6

Autosomal recessive osteopetrosis-6 (OPTB6) is a rare genetic disorder characterized by abnormally dense bone due to defective resorption of immature bone [8]. It occurs in childhood or adolescence, and the severity of the condition can vary among affected individuals [6].

The symptoms of OPTB6 include:

• Radiologic findings in childhood or adolescence
• Abnormally dense bones
• Defective resorption of immature bone

OPTB6 is caused by a homozygous mutation in the PLEKHM1 gene on chromosome 17q21 [1]. This condition is inherited in an autosomal recessive pattern, meaning that affected individuals have two copies of the mutated gene (one from each parent) and typically do not show signs and symptoms of the condition themselves.

It's worth noting that OPTB6 is a more severe form of osteopetrosis compared to other forms, such as autosomal dominant osteopetrosis [4]. The severity of the condition can vary among affected individuals, and it may be necessary for individuals with OPTB6 to undergo bone marrow transplantation or other treatments to manage their symptoms [5].

References:

[1] A number sign (#) is used with ... recessive osteopetrosis-6 (OPTB6) is caused by homozygous mutation in the PLEKHM1 gene (611466) on chromosome 17q21.

[4] Infantile onset osteopetrosis should be distinguished from the much milder autosomal dominant adult disease, the intermediated recessive form of osteopetrosis, and the carbonic anhydrase II deficiency syndrome, which is associated with renal tubular acidosis and less severe osteopetrosis.

[5] Gerritsen E. J., Vossen J

Autosomal Recessive Osteopetrosis (ARO) is a rare genetic disorder that affects the bones, causing them to become denser and more prone to fractures. The signs and symptoms of ARO can vary in severity and may include:

• Bone marrow failure: This is one of the classical features of the disease, which begins in early infancy or in fetal life [6].
• Fractures: Due to the increased bone density, bones are more prone to fractures, which can be a significant concern for individuals with ARO [7].
• Visual impairment: Visual impairment and peculiar eye motions, often known as exophthalmos, are frequently the first presenting symptoms [5].

In addition to these classical features, other signs and symptoms of ARO may include:

• Slow growth and short stature: Individuals with ARO may experience slow growth and short stature due to the disease's impact on bone development [8][9].
• Dental abnormalities: Dental abnormalities are another feature of ARO, which can affect tooth emergence and overall oral health [5].
• Enlarged liver: An enlarged liver is also a possible symptom of ARO, although its exact cause is not well understood [8][9].

It's essential to note that the severity and presentation of ARO symptoms can vary significantly from person to person. If you or someone you know has been diagnosed with ARO, it's crucial to work closely with a healthcare provider to manage the condition effectively.

References: [5] Apr 21, 2023 — Visual impairment and peculiar eye motions, often known as exophthalmos, are frequently the first presenting symptoms. [6] Bone marrow failure, fractures and visual impairment are the classical features of the disease, which begins in early infancy or in fetal life. [7] May 7, 2024 — Osteopetrosis is a condition that causes high bone density and abnormal bone growth. It also makes bones more prone to fractures. [8] Sep 26, 2024 — Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and ... [9] Sep 1, 2010 — Other features of autosomal recessive osteopetrosis can include slow growth and short stature, dental abnormalities, and an enlarged liver and ...

Autosomal recessive osteopetrosis (ARO) is a rare genetic disorder that affects the bones and can be challenging to diagnose. However, several diagnostic tests can help confirm the condition.

• Physical features: Physical examination may reveal characteristic features such as dense sclerotic bones, fractures, and other skeletal abnormalities [10].
• MRI of the brain: Magnetic Resonance Imaging (MRI) of the brain is recommended to assess the presence of cranial nerves involvement, hydrocephalus, and vascular abnormalities [6].
• Dual-Energy-X-rays: Dual-Energy-X-rays can help identify bone density changes and other skeletal abnormalities associated with ARO [6].
• Genetic testing: Genetic tests related to Osteopetrosis, Autosomal Recessive 6; 8, PLEKHM1 - NGS including CNV analysis can confirm the diagnosis by identifying mutations in the relevant genes [9].
• Laboratory findings: Laboratory findings such as increased creatinine kinase BB and tartrate-resistant acid phosphatase can aid in diagnosis [11].

It's essential to note that a combination of these diagnostic tests may be necessary to confirm the diagnosis of autosomal recessive osteopetrosis 6. A thorough clinical evaluation, including physical examination, medical history, and radiographic studies, is also crucial for accurate diagnosis.

References: [6] MRI of the brain should be performed to assess the presence of cranial nerves involvement, hydrocephalus, and vascular abnormalities. [9] Genetic tests related with Osteopetrosis, Autosomal Recessive 6; 8, PLEKHM1 - NGS including CNV analysis [10] Severe - autosomal recessive inheritance pattern (ARO – Autosomal Recessive Osteopetrosis): Presenting at birth or in the first few months. [11] Intermediate autosomal recessive osteopetrosis is the result of a loss of function mutation in CAII, the gene responsible for the production of the carbonic anhydrase II protein.

Treatment Options for Autosomal Recessive Osteopetrosis

Autosomal recessive osteopetrosis (ARO) is a severe inherited bone disease that requires prompt and effective treatment to manage its symptoms and prevent complications. While there is no cure for ARO, various drug treatments have been explored to alleviate the condition.

Vitamin-D Supplements

One of the potential treatments for ARO is vitamin-D supplements. Research suggests that these supplements can help stimulate dormant osteoclasts, thereby promoting bone resorption [6]. This approach may be beneficial in managing the disease's symptoms and improving quality of life.

Corticosteroids

Another treatment option for ARO is corticosteroids. These medications have been used to manage various conditions, including autoimmune disorders and inflammatory diseases. In the context of ARO, corticosteroids may help reduce inflammation and alleviate symptoms [6].

While these treatments show promise, it's essential to note that each patient's response to treatment may vary. Management and treatment plans should be tailored to individual needs, taking into account factors such as disease severity, age, and overall health.

References: [6] Oct 7, 2022 — Vitamin-D supplements: Appear to help by stimulating dormant osteoclasts, thus stimulating bone resorption · Corticosteroids: Have also been used ...

The differential diagnosis for autosomal recessive osteopetrosis (ARO) includes conditions that can result in diffuse osteosclerosis. Such disorders may be congenital diseases.

Some of the conditions that need to be considered in the differential diagnosis of ARO include:

• Congenital diseases that can lead to similar osteosclerosis
• Other rare genetic disorders that affect bone density

It's worth noting that a complete blood count with differential, as well as other diagnostic tests, may be necessary to rule out these conditions and confirm a diagnosis of ARO.

[6]