NGLY1 deficiency: Difference between revisions

Revision as of 06:53, 16 February 2025

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.

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.

Related Pages

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-'''NGLY1 deficiency''' is a rare genetic disorder characterized by a variety of symptoms, including developmental delay, movement disorder, and liver disease. It is caused by mutations in the [[NGLY1]] gene, which is responsible for producing an enzyme that helps break down and recycle proteins in cells.
+{{DISPLAYTITLE:NGLY1 deficiency}}
-== Symptoms and Signs ==
+== NGLY1 Deficiency ==
-The symptoms of NGLY1 deficiency can vary widely among affected individuals. Common symptoms include [[developmental delay]], [[movement disorder]], and [[liver disease]]. Other symptoms can include seizures, abnormal eye movements, and a lack of tears.
+[[File:Protein_NGLY1_PDB_2ccq.png|thumb|right|Structure of the NGLY1 protein.]]
+'''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.
-== Causes ==
+== Clinical Features ==
-NGLY1 deficiency is caused by mutations in the NGLY1 gene. This gene provides instructions for making an enzyme that is involved in the process of breaking down and recycling proteins in cells. When the NGLY1 gene is mutated, the enzyme's activity can be reduced or eliminated, leading to the symptoms of NGLY1 deficiency.
+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 ==
+[[File:Protein_NGLY1_PDB_2ccq.png|thumb|left|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.
 == Diagnosis ==
-Diagnosis of NGLY1 deficiency is based on the presence of characteristic symptoms, a detailed patient history, a thorough clinical evaluation, and a variety of specialized tests. These tests can include genetic testing, which can identify mutations in the NGLY1 gene.
+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.
-== Treatment ==
+== Management ==
-There is currently no cure for NGLY1 deficiency. Treatment is symptomatic and supportive, and may include physical therapy, occupational therapy, and medications to manage symptoms.
+Currently, there is no cure for NGLY1 deficiency. Management focuses on symptomatic treatment and supportive care, which may include:
-== Prognosis ==
+* Physical therapy for motor skills
-The prognosis for individuals with NGLY1 deficiency varies. Some individuals have a mild form of the disease and live into adulthood, while others have a more severe form and may not survive past childhood.
+* Anticonvulsants for seizure control
+* Nutritional support
+* Management of liver dysfunction
-== See also ==
+== Research ==
-* [[Genetic disorder]]
+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.
-* [[Rare disease]]
-* [[NGLY1]]
-== References ==
+== Related Pages ==
-<references />
+* [[Genetic disorders]]
+* [[Endoplasmic reticulum-associated degradation]]
+* [[Autosomal recessive inheritance]]
 [[Category:Genetic disorders]]
 [[Category:Rare diseases]]
-{{stub}}