Rare Immunology News

Disease Profile

GMPPA-CDG

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

no.svg

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

no.svg

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.

no.svg

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

no.svg

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.

no.svg

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.

no.svg

Not applicable

no.svg

Summary

GMPPAcongenital disorder of glycosylation (GMPPA-CDG) is a rare disease, part of the group of congenital disorders of glycosylation. It is characterized by lack of tears (alacrima), difficulty in swallowing due to problems in the esophagus muscle (achalasia), and intellectual disability, starting at birth or in early infancy. More variable features include low muscle tone (hypotonia), gait abnormalities, differently sized pupils (anisocoria), and vision or hearing problems. The disorder is very similar to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency. It is caused by a mutation in the GMPPA gene and is inherited in an autosomal recessive way.[1][2] Treatment is directed to the symptoms and may involve using artificial tears, medication, balloon dilation or surgery to correct the defect in the esophagus, and physical therapy.[3][4]

Symptoms

Signs and symptoms may include:[1][2]

  • Alacrima (reduced or absent tears production)
  • Feeding difficulties due to achalasia
  • Delayed psychomotor development with speech delay
  • Poor muscle tone
  • Gait abnormalities
  • Spasticity
  • Nasal speech
  • Visual problems
  • Hearing impairment
  • Decreased sweating
  • Postural hypotension
  • Anisocoria
  • Skin thickening (hyperkeratosis).

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
5%-29% of people have these symptoms
Anisocoria
Asymmetric pupil sizes
Asymmetry of the pupils
Unequal pupil size

[ more ]

0009916
Gait disturbance
Abnormal gait
Abnormal walk
Impaired gait

[ more ]

0001288
Generalized hypotonia
Decreased muscle tone
Low muscle tone

[ more ]

0001290
Hearing impairment
Deafness
Hearing defect

[ more ]

0000365
Hyperkeratosis
0000962
Hypohidrosis
Decreased ability to sweat
Decreased sweating
Sweating, decreased

[ more ]

0000966
Nasal speech
Nasal voice
0001611
Nystagmus
Involuntary, rapid, rhythmic eye movements
0000639
Orthostatic hypotension
Decrease in blood pressure upon standing up
0001278
Sensory impairment
0003474
Strabismus
Cross-eyed
Squint
Squint eyes

[ more ]

0000486
Percent of people who have these symptoms is not available through HPO
Achalasia
0002571
Alacrima
Absence of tears in the eyes
Absent tear secretion

[ more ]

0000522
Autosomal recessive inheritance
0000007
Dysphagia
Poor swallowing
Swallowing difficulties
Swallowing difficulty

[ more ]

0002015
Feeding difficulties
Feeding problems
Poor feeding

[ more ]

0011968
Global developmental delay
0001263
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation

[ more ]

0001249

Cause

GMPPAcongenital disorder of glycosylation is caused by mutations in the GMPPA gene. The GMPPA gene is involved in the production of N-linked oligosaccharides. N-linked glycosylation is the process of attaching a sugar (glycan) to a protein, which results in a structure known as a glycoprotein. The glycosylation process is important for the proper functioning of proteins.[5]

Treatment

There are only few cases described in the literature and there is no established treatment. Alacrima (lack of tears) may be treated with topical lubricants (such as artificial tears or ointments), and, if needed, with a procedure that drains tears from the eyes (punctal occlusion). The symptoms of alacrima typically improve with punctal occlusion.There are only a few cases described and there is not an established treatment. Achalasia is typically managed with surgical correction. The symptoms in patients with achalasia may be improved partially with pneumatic dilatation (also called balloon dilation). If the procedure does not improve the symptoms, other surgeries may be recommended.[2][6]

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    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.

    In-Depth Information

    • 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. Alacrima, achalasia, and mental retardation syndrome. OMIM. May, 2013; https://www.omim.org/entry/615510.
      2. Koehler K & cols. Mutations in GMPPA cause a glycosylation disorder characterized by intellectual disability and autonomic dysfunction. Am. J. Hum. Genet. 2013; 93:727-734. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791256/.
      3. Spechler SJ. Patient information: Achalasia (Beyond the Basics). UpToDate. February, 2016; https://www.uptodate.com/contents/achalasia-beyond-the-basics.
      4. DeAngelis DD. Alacrima. Medscape Reference. 2014; https://emedicine.medscape.com/article/1210539-overview.
      5. GMPPA GDP-mannose pyrophosphorylase A [ Homo sapiens (human) ]. NCBI. April, 2016; https://www.ncbi.nlm.nih.gov/gene/29926.
      6. Boston BA & Marks DL. Allgrove (AAA) Syndrome. Medscape Reference. February 27, 2013; https://emedicine.medscape.com/article/919360-treatment.

      Rare Immunology News