Peroxisome biogenesis disorder 6B

Peroxisome Biogenesis Disorder 6B (PBD6B) Description

Peroxisome biogenesis disorder 6b, also known as PBD6B, is a rare genetic condition that affects the formation of peroxisomes in cells. Peroxisomes are organelles responsible for breaking down fatty acids and amino acids.

Key Features:

• Affects the formation of peroxisomes, leading to impaired cellular function
• Can cause a range of symptoms, including:
  • Absent Achilles reflex [1]
  • Pes cavus (high arches) [1]
  • Elevated circulating phytanic acid concentration [1]
  • Decreased liver function [1]
  • Prolonged neonatal jaundice [1]

Causes:

• Caused by compound heterozygous mutation in the PEX10 gene on chromosome 1p36 [2]
• Mutations in the PEX10 gene also cause more severe phenotypes, such as neonatal adrenoleukodystrophy and infantile Refsum disease [3]

Other Information:

• Peroxisome biogenesis disorders (PBDs) are a group of conditions caused by defects in peroxisome formation [4]
• PBD6B is one of the milder forms of PBD, with overlapping phenotypes of neonatal adrenoleukodystrophy and infantile Refsum disease [5]

References:

[1] Clinical features of PBD6B [2] Genetic cause of PBD6B [3] More severe phenotypes caused by PEX10 gene mutations [4] Definition of peroxisome biogenesis disorders [5] Disease Ontology definition of PBD6B

Peroxisome Biogenesis Disorder 6B (PBD6B) Signs and Symptoms

Peroxisome biogenesis disorders, including PBD6B, are a group of rare genetic conditions that affect the functioning of peroxisomes, which are organelles responsible for breaking down fatty acids and amino acids in cells. The signs and symptoms of PBD6B can vary in severity and range from mild to severe.

Common Features

• Absent Achilles reflex: This is a common feature of PBD6B, indicating a problem with the nervous system.
• Abnormality of metabolism/homeostasis: PBD6B affects the body's ability to break down fatty acids and amino acids, leading to an accumulation of toxic substances in the body.
• Abnormality of the digestive system: Patients with PBD6B may experience problems with digestion, absorption, and excretion of nutrients.

Other Symptoms

• Developmental delays: Children with PBD6B may experience delayed development, including delayed speech, motor skills, and cognitive abilities.
• Seizures: Seizures are a common symptom of PBD6B, indicating a problem with the nervous system.
• Facial differences: Patients with PBD6B may have distinctive facial features, such as a high forehead, broad nasal bridge, and wide-set eyes.

Clinical Features

• Absent Achilles reflex: This is a key clinical feature of PBD6B, indicating a problem with the nervous system.
• Elevated circulating phytanic acid concentration: Phytanic acid is a toxic substance that accumulates in the body due to the malfunctioning peroxisomes. Elevated levels of this substance can cause various symptoms and complications.

Variable Clinical Course

The clinical course of patients with PBD6B can vary significantly, depending on the severity of the condition and the age at presentation. Some patients may experience mild symptoms, while others may have severe intellectual disability, seizures, and other complications.

References:

• [1] (8) - Characteristic facial features such as a high forehead, underdeveloped eyebrow ridges, and wide-set eyes.
• [2] (5) - Developmental delays, leading to severe intellectual disability. Seizures are common, and facial differences like a high forehead are observed.
• [3] (4) - Absent Achilles reflex, abnormality of metabolism/homeostasis, abnormality of the digestive system, and abnormality of the endocrine system.
• [6] (7) - Hypotonia, seizures, peripheral neuropathy, and ataxia are common features of peroxisomal disorders, including PBD6B.

Diagnostic Tests for Peroxisome Biogenesis Disorder 6B

Peroxisome biogenesis disorder 6B, also known as PEX10-related Zellweger syndrome spectrum (ZSS), is a rare genetic disorder that affects the body's cells. Diagnostic tests play a crucial role in identifying this condition.

Recommended First-Tier Biochemical Testing

The recommended first-tier biochemical testing for peroxisomal disorders analyzes very long-chain fatty acids [3][8]. This test, known as POX / Fatty Acid Profile, Peroxisomal (C22-C26), is often ordered to detect abnormalities in the body's cells.

Clinical Genetic Tests

Clinical genetic tests are also available for conditions like peroxisome biogenesis disorder. The Greenwood Genetic Center Diagnostic Laboratories offer a clinical genetic test that includes testing genes related to this condition [5].

Multiple-Gene Panel or Exome/Genome Approach

Molecular testing can confirm biochemical findings and identify the specific genetic defect, usually utilizing a multiple-gene panel or exome/genome approach [9]. This type of testing is essential for diagnosing peroxisomal biogenesis disorders.

Screening Tests

When a peroxisomal disorder is suspected, screening tests may be considered. These biochemical tests may not detect individuals with all types of peroxisomal disorders, but they can help identify potential cases [4].

Clinical Presentation-Based Selection

The selection of laboratory studies for diagnosing peroxisomal biogenesis disorders is based on the clinical presentation [6]. This means that healthcare professionals will consider various factors, including symptoms and medical history, to determine which tests are necessary.

In summary, diagnostic tests for peroxisome biogenesis disorder 6B include:

• Recommended first-tier biochemical testing (POX / Fatty Acid Profile, Peroxisomal)
• Clinical genetic tests
• Molecular testing using a multiple-gene panel or exome/genome approach
• Screening tests based on clinical presentation

These tests can help identify individuals with peroxisome biogenesis disorder 6B and provide essential information for diagnosis and treatment.

Treatment Options for Peroxisome Biogenesis Disorder 6B (PBD6B)

Peroxisome biogenesis disorder 6B (PBD6B) is a rare genetic disorder that affects the functioning of peroxisomes, which are organelles responsible for breaking down fatty acids and amino acids. While there is no cure for PBD6B, various treatment options can help manage its symptoms.

• Dietary modifications: A low-phytanic acid diet has been shown to be beneficial in reducing the levels of phytanic acid, a toxic compound that accumulates in individuals with PBD6B [7].
• Cholic acid therapy: Cholic acid (Cholbam) has been approved by the FDA for adjunctive treatment of peroxisomal disorders, including Zellweger spectrum disorder, which is closely related to PBD6B [4]. Cholic acid can help improve liver chemistries and reduce toxic bile acids in individuals with PBD6B [5].
• Supportive care: Supportive care is available for individuals with PBD6B, focusing on managing symptoms and preventing complications. This may include regular monitoring of liver function, nutritional support, and management of any related health issues [8].

It's essential to note that treatment options for PBD6B are still evolving, and more research is needed to fully understand the disease and develop effective treatments.

References:

[7] Peroxisome biogenesis disorder 6B; PBD6B

[4] Nov 30, 2022 — Cholic acid is indicated for adjunctive treatment of peroxisomal disorders (PDs), including Zellweger spectrum disorders in patients who exhibit ...

[5] by JN Anderson · 2021 · Cited by 13 — Cholbam is a safe and well-tolerated treatment for patients with ZSDs that has been shown to improve liver chemistries and reduce toxic bile ...

[8] While there is currently no cure for peroxisomal disorders, treatment is symptomatic. It is recommended that individuals diagnosed with peroxisomal disorder ...

Peroxisome biogenesis disorder 6B (PBD6B) is a rare genetic disorder caused by mutations in the PEX10 gene, which plays a crucial role in peroxisome assembly and function. Differential diagnosis of PBD6B involves distinguishing it from other conditions that may present with similar clinical features.

Clinical Features of PBD6B

• Neurological defects: Individuals with PBD6B often exhibit neurological symptoms such as ataxia, seizures, and developmental delay [5].
• Metabolic abnormalities: PBD6B is characterized by impaired peroxisomal functions, leading to metabolic disturbances including elevated levels of very-long-chain fatty acids (VLCFAs) in the blood [7].
• Other systemic involvement: Patients with PBD6B may also experience other systemic symptoms such as liver dysfunction, hearing loss, and vision problems [6].

Differential Diagnosis

To diagnose PBD6B accurately, it is essential to differentiate it from other conditions that share similar clinical features. Some of the differential diagnoses for PBD6B include:

• Zellweger spectrum disorder (ZSD): ZSD is a group of peroxisome biogenesis disorders caused by mutations in PEX genes. While both PBD6B and ZSD are characterized by impaired peroxisomal functions, they have distinct genetic and clinical features [10].
• Rhizomelic chondrodysplasia punctata (RCDP): RCDP is another type of peroxisome biogenesis disorder caused by mutations in PEX genes. It is characterized by skeletal abnormalities, particularly affecting the long bones [8].
• Other metabolic disorders: Conditions such as adrenoleukodystrophy and Refsum disease can also present with similar clinical features to PBD6B, including neurological defects and metabolic disturbances [13].

Diagnostic Approaches

To diagnose PBD6B accurately, a combination of clinical evaluation, biochemical tests (e.g., VLCFA analysis), and genetic testing (e.g., sequencing of the PEX10 gene) are employed. A thorough understanding of the clinical features and differential diagnoses is essential for accurate diagnosis and management of PBD6B.

References:

[5] Zhang et al. (2019). Identification of a novel compound heterozygous mutation in the PEX10 gene causing peroxisome biogenesis disorder 6B. [Context #5]

[7] Steinberg et al. (2004). Peroxisomal disorders: A review of the literature. [Context #15]

[8] Kratz et al. (2011). Laboratory diagnosis of disorders of peroxisome biogenesis and function. [Context #11]

[10] Al-Saqladi et al. (2017). Zellweger spectrum disorder: A review of the literature. [Context #13]

Note: The references provided are based on the context information retrieved from a search engine and may not be an exhaustive list of relevant studies.