Rare Dermatology News

Disease Profile

Deficiency of N-glycanase 1

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

#N/A

ICD-10

#N/A

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

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Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Congenital disorder of deglycosylation;CDDG; Congenital disorder of glycosylation type IV; CDG1V; Alacrimia-choreoathetosis-liver dysfunction syndrome;

Summary

Deficiency of N-glycanase 1 (NGLY1 deficiency) is a complex neurological syndrome in which there is a deficiency of an enzyme known as N-glycanase 1 (NGLY1). This enzyme normally helps the body remove proteins that are not functioning properly. The typical features of NGLY1 deficiency include abnormal tear production, a movement disorder (choreoathetosis), and liver disease. Additional features may include developmental delay, hypotonia (weak muscle tone), peripheral neuropathy , EEG abnormalities, and a small head size (microcephaly). The condition is caused by mutations in the N-glycanase 1 gene (NGLY1 gene) and is inherited in an autosomal recessive manner.[1][2]

Symptoms

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
1%-4% of people have these symptoms
Anhidrosis
Lack of sweating
Sweating dysfunction

[ more ]

0000970
Central sleep apnea
0010536
Corneal opacity
0007957
Decreased CSF/serum albumin ratio
0030978
Decreased sensory nerve conduction velocity
0003448
Delayed myelination
0012448
Elevated alpha-fetoprotein
0006254
Elevated brain choline level by MRS
0012706
Elevated hepatic transaminase
High liver enzymes
0002910
Facial hypotonia
Decreased facial muscle tone
Low facial muscle tone
Reduced facial muscle tone

[ more ]

0000297
Global developmental delay
0001263
Hepatomegaly
Enlarged liver
0002240
High myoinositol in brain by MRS
0025460
Hyperhidrosis
Excessive sweating
Increased sweating
Profuse sweating
Sweating
Sweating profusely
Sweating, increased

[ more ]

0000975
Hyperkinetic movements
Muscle spasms
0002487
Hypertelorism
Wide-set eyes
Widely spaced eyes

[ more ]

0000316
Hyporeflexia
Decreased reflex response
Decreased reflexes

[ more ]

0001265
Impaired oral bolus formation
0031146
Impaired oropharyngeal swallow response
0031162
Increased serum lactate
0002151
Intrinsic hand muscle atrophy
0008954
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference

[ more ]

0000252
Oral-pharyngeal dysphagia
0200136
Osteoporosis
0000939
Pain insensitivity
0007021
Ptosis
Drooping upper eyelid
0000508
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Reduced brain glutamine level by MRS
0030980
Reduced brain N-acetyl aspartate level by MRS
0012708
Respiratory distress
Breathing difficulties
Difficulty breathing

[ more ]

0002098
Restlessness
0000711
Scoliosis
0002650
Seizure
0001250
Short foot
Short feet
Small feet

[ more ]

0001773
Single transverse palmar crease
0000954
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Suck reflex
0030906
Percent of people who have these symptoms is not available through HPO
Action tremor
0002345
Alacrima
Absence of tears in the eyes
Absent tear secretion

[ more ]

0000522
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils

[ more ]

0000463
Athetosis
Involuntary writhing movements in fingers, hands, toes, and feet
0002305
Autosomal recessive inheritance
0000007
Brachycephaly
Short and broad skull
0000248
Chorea
0002072
Corneal ulceration
0012804
Decreased body weight
Decreased weight
Low body weight
Low weight
Weight less than 3rd percentile

[ more ]

0004325
Decreased CSF 5-hydroxyindolacetic acid
0025455
Decreased CSF albumin concentration
0025458
Dysmetria
Lack of coordination of movement
0001310
Fever
0001945
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Infantile onset
Onset in first year of life
Onset in infancy

[ more ]

0003593
Myoclonus
0001336
Narrow face
Decreased breadth of face
Decreased width of face

[ more ]

0000275
Pain
0012531
Perivascular spaces
0012520
Polyneuropathy
Peripheral nerve disease
0001271
Small hand
Disproportionately small hands
0200055
Sunken cheeks
Depressed cheeks
Hollow cheeks

[ more ]

0009938

Learn more

These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

Where to Start

  • Genetics Home Reference (GHR) contains information on Deficiency of N-glycanase 1. This website is maintained by the National Library of Medicine.
  • NGLY1.org has developed a handbook for patients, families and healthcare providers entitled "About NGLY1 Deficiency." NGLY1.org is a foundation dedicated to NGLY1 deficiency research, awareness and support.

    In-Depth Information

    • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
    • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
    • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 

      References

      1. Enns, Gregory, et al.. Mutations in NGLY1 Cause an Inherited Disorder of the Endoplasmic Reticulum-Associated Degradation (ERAD) Pathway. October, 2014; 16 (10):751-758. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4243708/. Accessed 9/9/2015.
      2. CONGENITAL DISORDER OF DEGLYCOSYLATION; CDDG. Online Mendelian Inheritance in Man (OMIM) # 615273. June 9, 2015; https://omim.org/entry/615273. Accessed 9/9/2015.

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