NGLY1 deficiency: Difference between revisions
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{{Infobox medical condition | |||
| name = NGLY1 deficiency | |||
| image = [[File:Protein_NGLY1_PDB_2ccq.png|alt=Protein NGLY1 PDB 2ccq]] | |||
| caption = Structure of the NGLY1 protein | |||
| synonyms = Congenital disorder of deglycosylation | |||
| pronounce = | |||
| specialty = [[Medical genetics]] | |||
| symptoms = Developmental delay, movement disorders, liver dysfunction, seizures | |||
| onset = Infancy | |||
| duration = Lifelong | |||
| causes = Mutations in the [[NGLY1]] gene | |||
| risks = | |||
| diagnosis = [[Genetic testing]], clinical evaluation | |||
| differential = Other congenital disorders of glycosylation | |||
| prevention = None | |||
| treatment = Supportive care, physical therapy | |||
| medication = | |||
| prognosis = Variable | |||
| frequency = Very rare | |||
| deaths = | |||
}} | |||
{{DISPLAYTITLE:NGLY1 deficiency}} | {{DISPLAYTITLE:NGLY1 deficiency}} | ||
'''NGLY1 deficiency''' is a rare genetic disorder caused by mutations in the [[NGLY1]] gene, which encodes the enzyme N-glycanase 1. This enzyme is responsible for the deglycosylation of misfolded glycoproteins in the [[endoplasmic reticulum]]-associated degradation (ERAD) pathway. The deficiency leads to a buildup of misfolded glycoproteins, resulting in a variety of clinical symptoms. | '''NGLY1 deficiency''' is a rare genetic disorder caused by mutations in the [[NGLY1]] gene, which encodes the enzyme N-glycanase 1. This enzyme is responsible for the deglycosylation of misfolded glycoproteins in the [[endoplasmic reticulum]]-associated degradation (ERAD) pathway. The deficiency leads to a buildup of misfolded glycoproteins, resulting in a variety of clinical symptoms. | ||
== Clinical Features == | == Clinical Features == | ||
Patients with NGLY1 deficiency typically present with a range of symptoms, including: | Patients with NGLY1 deficiency typically present with a range of symptoms, including: | ||
* Developmental delay | * Developmental delay | ||
* [[Hypotonia]] | * [[Hypotonia]] | ||
| Line 14: | Line 31: | ||
* [[Movement disorders]] | * [[Movement disorders]] | ||
* [[Alacrima]] (reduced tear production) | * [[Alacrima]] (reduced tear production) | ||
The severity and combination of symptoms can vary widely among affected individuals. | The severity and combination of symptoms can vary widely among affected individuals. | ||
== Genetics == | == Genetics == | ||
NGLY1 deficiency is inherited in an [[autosomal recessive]] manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. Carriers, who have only one copy of the mutation, typically do not show symptoms. | NGLY1 deficiency is inherited in an [[autosomal recessive]] manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. Carriers, who have only one copy of the mutation, typically do not show symptoms. | ||
== Pathophysiology == | == Pathophysiology == | ||
[[File:Protein_NGLY1_PDB_2ccq.png|thumb | [[File:Protein_NGLY1_PDB_2ccq.png|left|thumb|NGLY1 protein structure highlighting its active site.]] | ||
The NGLY1 enzyme plays a crucial role in the ERAD pathway by removing N-linked glycans from misfolded glycoproteins, allowing them to be degraded by the [[proteasome]]. In the absence of functional NGLY1, these glycoproteins accumulate, leading to cellular stress and dysfunction. | The NGLY1 enzyme plays a crucial role in the ERAD pathway by removing N-linked glycans from misfolded glycoproteins, allowing them to be degraded by the [[proteasome]]. In the absence of functional NGLY1, these glycoproteins accumulate, leading to cellular stress and dysfunction. | ||
== Diagnosis == | == Diagnosis == | ||
Diagnosis of NGLY1 deficiency is typically confirmed through genetic testing, which identifies mutations in the NGLY1 gene. Biochemical assays may also be used to assess enzyme activity. | Diagnosis of NGLY1 deficiency is typically confirmed through genetic testing, which identifies mutations in the NGLY1 gene. Biochemical assays may also be used to assess enzyme activity. | ||
== Management == | == Management == | ||
Currently, there is no cure for NGLY1 deficiency. Management focuses on symptomatic treatment and supportive care, which may include: | Currently, there is no cure for NGLY1 deficiency. Management focuses on symptomatic treatment and supportive care, which may include: | ||
* Physical therapy for motor skills | * Physical therapy for motor skills | ||
* Anticonvulsants for seizure control | * Anticonvulsants for seizure control | ||
* Nutritional support | * Nutritional support | ||
* Management of liver dysfunction | * Management of liver dysfunction | ||
== Research == | == Research == | ||
Research into NGLY1 deficiency is ongoing, with efforts focused on understanding the molecular mechanisms of the disease and developing potential therapies. Gene therapy and enzyme replacement therapy are areas of active investigation. | Research into NGLY1 deficiency is ongoing, with efforts focused on understanding the molecular mechanisms of the disease and developing potential therapies. Gene therapy and enzyme replacement therapy are areas of active investigation. | ||
== See also == | |||
== | |||
* [[Genetic disorders]] | * [[Genetic disorders]] | ||
* [[Endoplasmic reticulum-associated degradation]] | * [[Endoplasmic reticulum-associated degradation]] | ||
* [[Autosomal recessive inheritance]] | * [[Autosomal recessive inheritance]] | ||
[[Category:Genetic disorders]] | [[Category:Genetic disorders]] | ||
[[Category:Rare diseases]] | [[Category:Rare diseases]] | ||
Revision as of 03:51, 8 April 2025
Editor-In-Chief: Prab R Tumpati, MD
Obesity, Sleep & Internal medicine
Founder, WikiMD Wellnesspedia &
W8MD medical weight loss NYC and sleep center NYC
| NGLY1 deficiency | |
|---|---|
| |
| Synonyms | Congenital disorder of deglycosylation |
| Pronounce | |
| Specialty | Medical genetics |
| Symptoms | Developmental delay, movement disorders, liver dysfunction, seizures |
| Complications | N/A |
| Onset | Infancy |
| Duration | Lifelong |
| Types | N/A |
| Causes | Mutations in the NGLY1 gene |
| Risks | |
| Diagnosis | Genetic testing, clinical evaluation |
| Differential diagnosis | Other congenital disorders of glycosylation |
| Prevention | None |
| Treatment | Supportive care, physical therapy |
| Medication | |
| Prognosis | Variable |
| Frequency | Very rare |
| Deaths | |
NGLY1 deficiency is a rare genetic disorder caused by mutations in the NGLY1 gene, which encodes the enzyme N-glycanase 1. This enzyme is responsible for the deglycosylation of misfolded glycoproteins in the endoplasmic reticulum-associated degradation (ERAD) pathway. The deficiency leads to a buildup of misfolded glycoproteins, resulting in a variety of clinical symptoms.
Clinical Features
Patients with NGLY1 deficiency typically present with a range of symptoms, including:
- Developmental delay
- Hypotonia
- Seizures
- Liver dysfunction
- Movement disorders
- Alacrima (reduced tear production)
The severity and combination of symptoms can vary widely among affected individuals.
Genetics
NGLY1 deficiency is inherited in an autosomal recessive manner. This means that an affected individual must inherit two copies of the mutated gene, one from each parent. Carriers, who have only one copy of the mutation, typically do not show symptoms.
Pathophysiology
The NGLY1 enzyme plays a crucial role in the ERAD pathway by removing N-linked glycans from misfolded glycoproteins, allowing them to be degraded by the proteasome. In the absence of functional NGLY1, these glycoproteins accumulate, leading to cellular stress and dysfunction.
Diagnosis
Diagnosis of NGLY1 deficiency is typically confirmed through genetic testing, which identifies mutations in the NGLY1 gene. Biochemical assays may also be used to assess enzyme activity.
Management
Currently, there is no cure for NGLY1 deficiency. Management focuses on symptomatic treatment and supportive care, which may include:
- Physical therapy for motor skills
- Anticonvulsants for seizure control
- Nutritional support
- Management of liver dysfunction
Research
Research into NGLY1 deficiency is ongoing, with efforts focused on understanding the molecular mechanisms of the disease and developing potential therapies. Gene therapy and enzyme replacement therapy are areas of active investigation.
