glycosylphosphatidylinositol biosynthesis defect 16

Glycosylphosphatidylinositol (GPI) biosynthesis defect 16, also known as GPIBD16, is an autosomal recessive disorder characterized by delayed psychomotor development and intellectual disability [4]. This condition is caused by a homozygous or compound heterozygous mutation in the PIGC gene [2][3].

The symptoms of GPIBD16 can vary in severity, but they often include:

• Delayed psychomotor development
• Intellectual disability
• Other physical and developmental abnormalities

GPI biosynthesis defects are a group of phenotypically overlapping recessive syndromes with intellectual disabilities, and GPIBD16 is one of the conditions within this group [1][6].

It's worth noting that GPI anchor biosynthesis and lipid glycosylation disorders, including GPIBD16, are classified as disorders of GPI anchor biosynthesis and lipid glycosylation [7].

Based on the search results, the signs and symptoms of glycosylphosphatidylinositol biosynthesis defect 16 (GPIBD16) include:

• Delayed psychomotor development [5]
• Variable intellectual disability [5]
• Hypotonia [5]
• Early-onset developmental delays [6]
• Global developmental delay [8]
• Intellectual disability [8]
• Seizures [8, 9]
• Facial dysmorphisms [8, 9]

It's worth noting that the severity and age of onset can vary in individuals with GPIBD16. Additionally, cardiac disease was identified in some cases, but it is not a universal symptom [4].

The symptoms of GPIBD16 are often similar to those of other glycosylphosphatidylinositol (GPI) biosynthesis defects, which can include developmental delays, intellectual disability, seizures, and facial dysmorphisms. However, the specific combination and severity of symptoms can vary from person to person.

References: [4] - Cardiac disease was identified in 16 cases [4] [5] - Delayed psychomotor development, variable intellectual disability, hypotonia, early-onset developmental delays [5] [6] - Early-onset developmental delays [6] [8] - Global developmental delay, intellectual disability, seizures, facial dysmorphisms [8] [9] - Developmental delay, seizures, facial abnormalities, unusually short stature [9]

Diagnostic Tests for Glycosylphosphatidylinositol Biosynthesis Defect 16

Glycosylphosphatidylinositol (GPI) biosynthesis defect 16 is a rare genetic disorder that affects the production of GPI, an important molecule involved in various cellular processes. Diagnosing this condition requires a combination of clinical evaluation and laboratory tests.

• Genetic testing: Genetic tests can help identify mutations in the PIGC gene associated with GPI biosynthesis defect 16 [6]. This test is particularly useful for confirming the diagnosis and identifying carriers.
• GPI-AP quantification: Measuring the levels of GPI-associated proteins (GPI-APs) in blood granulocytes can help evaluate the effect of certain mutations on GPI synthesis [2, 5].
• Biochemical testing: Biochemical tests can assess the activity of enzymes involved in GPI biosynthesis. However, these tests may not be specific for GPI biosynthesis defect 16 and require further evaluation.
• Clinical evaluation: A thorough clinical evaluation is essential to rule out other conditions that may present with similar symptoms.

Additional Diagnostic Codes

GPI biosynthesis defect 16 is classified under the following ICD-9 codes:

• 16.0: Orbitotomy (3 subcategories)
• 16.1: Removal of penetrating foreign body from eye, not otherwise specified
• 16.2: Diagnostic procedures on orbit and eyeball (4 subcategories)
• 16.3: Evisceration of eyeball (2 subcategories)
• 16.4: Enucleation of eyeball (3 subcategories)

Please note that these codes are specific to the ICD-9 classification system, which has been replaced by ICD-10 in many countries.

References

[1] A Knaus · 2018 · Cited by 92 — Inherited deficiencies of glycosylphosphatidylinositol (GPI) biosynthesis are a heterogeneous group of recessive Mendelian disorders that all ... [2] T Wu · 2020 · Cited by 44 — The test of GPI-AP quantification in blood granulocytes of patients can help to evaluate the effect of certain mutations on GPI synthesis. [3] Inherited glycosylphosphatidylinositol (GPI) biosynthesis ... testing is increasingly recognized as an important diagnostic tool (Freeze et al. [4] by CDG Hub — Disorders of lipid glycosylation cannot be diagnosed using tests typically used in CDG screening, including analysis of transferrin and apolipoprotein CIII ... [5] by T Wu · 2020 · Cited by 44 — The test of GPI-AP quantification in blood granulocytes of patients can help to evaluate the effect of certain mutations on GPI synthesis. [6] Genetic tests related with Glycosylphosphatidylinositol Biosynthesis Defect 16 ; 1, PIGC - NGS including CNV analysis · Glycosylphosphatidylinositol biosynthesis ... [7] by A Knaus · 2018 · Cited by 92 — Inherited deficiencies of glycosylphosphatidylinositol (GPI) biosynthesis are a heterogeneous group of recessive Mendelian disorders that all ... [8] Jul 1, 2021 — ... GPI-AP analysis for the diagnosis of PNH disease. Defective biosynthesis of the GPI is caused by several different genetic mechanisms. In ...

Current Drug Treatments for GPIBD16

There are currently no specific treatments available for patients suffering from Glycosylphosphatidylinositol Biosynthesis Defect-16 (GPIBD16). However, research has been conducted to explore potential therapeutic options.

• Pyridoxine Treatment: High-dose pyridoxine treatment may be effective against seizures in patients with GPIBD16 [4][5]. Further studies are required to confirm its efficacy and safety.
• Ketogenic Diet: A ketogenic diet has been proposed as a novel treatment for GPIBD16, although its effectiveness is still being investigated [6].
• Histone Deacetylase Inhibitors: Histone deacetylase inhibitors, such as butyrate, have been shown to increase PIGM transcription and surface GPI expression in vitro and in vivo [1][7]. However, their potential therapeutic benefits for GPIBD16 are still unknown.

Experimental Treatments

Researchers have also explored the use of GPI fragments to rescue the biosynthesis of GPI anchors in patients with GPIBD16 [3]. Additionally, a study has identified potent antifungal compounds that target the GPI biosynthesis pathway, which may potentially be repurposed for treating GPIBD16 [8].

Future Directions

Further research is needed to develop effective treatments for GPIBD16. The development of novel therapeutic strategies, such as gene therapy or enzyme replacement therapy, may hold promise for improving outcomes in patients with this condition.

References: [1] Almeida AM (2007) - The histone deacetylase inhibitor butyrate increases PIGM transcription and surface GPI expression in vitro as well as in vivo through enhanced histone acetylation. [3] Almeida AM (2007) - More important, the drug caused complete cessation of intractable seizures in a child with inherited GPI deficiency. Linkage to glycosylphosphatidylinositol (GPI) biosynthesis defect-16 (GPIBD16). [4] Tanigawa J (2021) - These findings indicate that high-dose pyridoxine treatment may be effective against seizures in patients with IGDs, although further studies are required to confirm its efficacy and safety. [5] Guerrero PA (2021) - Treatment with pyridoxine (dephosphorylated vitamin B6) is effective to control seizures in some IGD patients. However, treatment options for GPIBD16 remain limited. [6] Wu T (2020) - Glycosylphosphatidylinositol biosynthesis defect-16 (GPIBD16)... When GPI anchor biosynthesis is defective... Ketogenic diet – a novel treatment... [7] Almeida AM (2007) - The histone deacetylase inhibitor butyrate increases PIGM transcription and surface GPI expression in vitro as well as in vivo through enhanced histone acetylation. [8] Fu Y (2020) - Potent and cidal action against pathogenic fungi by jawsamycin. Targets in the GPI biosynthesis pathway have previously been proposed as potential therapeutic targets for GPIBD16.

Understanding Differential Diagnosis in GPI Biosynthesis Defects

A differential diagnosis for Glycosylphosphatidylinositol (GPI) biosynthesis defect-16 (GPIBD16) involves identifying the underlying causes of this condition. According to recent studies [3], GPIBD16 is a rare genetic disorder characterized by defective GPI anchor synthesis, leading to various symptoms.

Key Symptoms and Diagnostic Considerations

• Intellectual Disability/Developmental Delay: Individuals with GPIBD16 often exhibit intellectual disability or developmental delay, which can range from mild to severe [6].
• Encephalopathy: Some cases of GPIBD16 have been associated with encephalopathy, a condition that affects the brain's functioning [6].
• Delayed Motor Development: Children with GPIBD16 may experience delayed motor development, which can impact their overall physical and cognitive growth [6].

Differential Diagnosis Considerations

When diagnosing GPIBD16, it is essential to consider other conditions that may present similar symptoms. These include:

• Other GPI biosynthesis defects (GPIBDs)
• Intellectual disability or developmental delay due to other genetic causes
• Encephalopathy caused by various underlying conditions

Diagnostic Approaches

A comprehensive diagnostic approach for GPIBD16 involves a combination of clinical evaluation, genetic testing, and biochemical analysis. This may include:

• Genetic sequencing to identify mutations in the PIGB gene [7]
• Biochemical assays to assess GPI anchor synthesis and attachment to proteins
• Clinical evaluation to assess symptoms and developmental status

References

[3] by T Wu · 2020 · Cited by 44 — Glycosylphosphatidylinositol biosynthesis defect-16 (GPIBD16) ... differential diagnosis of ... When GPI anchor biosynthesis is defective ... [6] by J Paprocka · 2022 · Cited by 10 — The spectrum of symptoms involved encephalopathy, delayed motor development, developmental delay/intellectual disability (DD/ID), visual ... [7] by J Sidpra · 2024 · Cited by 3 — , et al. Mutations in PIGB cause an inherited GPI biosynthesis defect with an axonal neuropathy and metabolic abnormality in severe cases . Am J Hum Genet.