National Center for Advancing and Translational Sciences Genetic and Rare Diseases Information Center, a program of the National Center for Advancing and Translational Sciences

GMPPA-CDG


This disease is grouped under:
GMPPA-congenital 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]
Last updated: 4/6/2016
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).
Last updated: 4/6/2016

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.

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Medical Terms Other Names
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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
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Last updated: 7/1/2020
GMPPA-congenital 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]
Last updated: 4/6/2016
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]
Last updated: 4/6/2016

If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals. You may also want to contact a university or tertiary medical center in your area, because these centers tend to see more complex cases and have the latest technology and treatments.

If you can’t find a specialist in your local area, try contacting national or international specialists. They may be able to refer you to someone they know through conferences or research efforts. Some specialists may be willing to consult with you or your local doctors over the phone or by email if you can't travel to them for care.

You can find more tips in our guide, How to Find a Disease Specialist. We also encourage you to explore the rest of this page to find resources that can help you find specialists.

Healthcare Resources

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

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. 

Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.

  1. Alacrima, achalasia, and mental retardation syndrome. OMIM. May, 2013; http://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. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3791256/.
  3. Spechler SJ. Patient information: Achalasia (Beyond the Basics). UpToDate. February, 2016; http://www.uptodate.com/contents/achalasia-beyond-the-basics.
  4. DeAngelis DD. Alacrima. Medscape Reference. 2014; http://emedicine.medscape.com/article/1210539-overview.
  5. GMPPA GDP-mannose pyrophosphorylase A [ Homo sapiens (human) ]. NCBI. April, 2016; http://www.ncbi.nlm.nih.gov/gene/29926.
  6. Boston BA & Marks DL. Allgrove (AAA) Syndrome. Medscape Reference. February 27, 2013; http://emedicine.medscape.com/article/919360-treatment.