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

Maternal hyperphenylalaninemia



Other Names:
Maternal phenylketonuria; MPKU; Hyperphenylalaninemic embryopathy; Maternal phenylketonuria; MPKU; Hyperphenylalaninemic embryopathy; Maternal PKU; Phenylketonuric embryopathy See More
Categories:

The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.
orphanet

Orpha Number: 2209

Definition
A rare disorder of phenylalanine metabolism, an inborn error of amino acid metabolism, characterized by the development of microcephaly, growth retardation, congenital heart disease, facial dysmorphism and intellectual disability in nonphenylketonuric offspring of mothers with excess phenylalanine (Phe) concentrations.

Epidemiology
The incidence of maternal phenylketonuria (PKU) in Europe is estimated to be 1/10,000. Increased survival and improved health among females with treated PKU, thanks to neonatal screening, has increased the number of potential pregnancies with a risk of elevated maternal Phe.

Clinical description
Hyperphenylalaninemia is classified by serum phenylalanine concentrations of more than 1,200 micromol/L (classic PKU; see this term) or less than 600 micromol/L (hyperphenylalaninemia; see this term), between 600 and 1.200 micromol/L as mild PKU. Maternal phenylketonuria syndrome in offspring has been shown to result in intrauterine and postnatal growth retardation with associated low birth weight, microcephaly, and intellectual disability. Congenital heart malformation is also found and may include double-chambered right ventricle, tetralogy of Fallot, and ventricular septal defects (see these terms). In severe cases, facial dysmorphism may also occur with various features reported including receding forehead, fused eyes, strabismus, dysplastic ear helices, high palate ,underdeveloped philtrum, anteverted nostrils, broad flat nasal bridge, deviated nasal septum, micrognathia, and ptosis. Optimal maternal Phe concentrations should be strictly maintained throughout pregnancy to reduce the risk of these abnormalities. This can be achieved by minimal Phe intake, along with tyrosine-enriched supplements. Studies have also shown that dietary treatment to control Phe concentrations can prevent the disorder if started before conception.

Etiology
Abnormally high maternal Phe concentrations underlie the clinical effects found in children with this disorder. PKU and hyperphenylalaninemia are caused by mutations in the PAH gene (12q22-q24.2).

Genetic counseling
Phenylketonuria is transmitted in an autosomal recessive manner. Affected children will therefore mostly be heterozygous carriers or non-carriers of the defect.

Visit the Orphanet disease page for more resources.
Last updated: 1/1/2015

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.

Showing of 31 |
Medical Terms Other Names
Learn More:
HPO ID
30%-79% of people have these symptoms
Abnormal facial shape
Unusual facial appearance
0001999
Coarctation of aorta
Narrowing of aorta
Narrowing of the aorta
[ more ]
0001680
Global developmental delay 0001263
Hypoplastic left heart
Underdeveloped left heart
0004383
Intellectual disability
Mental deficiency
Mental retardation
Mental retardation, nonspecific
Mental-retardation
[ more ]
0001249
Intrauterine growth retardation
Prenatal growth deficiency
Prenatal growth retardation
[ more ]
0001511
Microcephaly
Abnormally small skull
Decreased circumference of cranium
Decreased size of skull
Reduced head circumference
Small head circumference
[ more ]
0000252
5%-29% of people have these symptoms
Anteverted nares
Nasal tip, upturned
Upturned nasal tip
Upturned nose
Upturned nostrils
[ more ]
0000463
Double outlet right ventricle 0001719
High palate
Elevated palate
Increased palatal height
[ more ]
0000218
Hyperactivity
More active than typical
0000752
Hypoplasia of the corpus callosum
Underdevelopment of part of brain called corpus callosum
0002079
Long philtrum 0000343
Micrognathia
Little lower jaw
Small jaw
Small lower jaw
[ more ]
0000347
Seizure 0001250
Tetralogy of Fallot 0001636
Ventricular septal defect
Hole in heart wall separating two lower heart chambers
0001629
Wide nasal bridge
Broad nasal bridge
Broad nasal root
Broadened nasal bridge
Increased breadth of bridge of nose
Increased breadth of nasal bridge
Increased width of bridge of nose
Increased width of nasal bridge
Nasal bridge broad
Wide bridge of nose
Widened nasal bridge
[ more ]
0000431
1%-4% of people have these symptoms
Abnormal renal morphology
Abnormally shaped kidney
Kidney malformation
Kidney structure issue
Structural kidney abnormalities
[ more ]
0012210
Bifid distal phalanx of the thumb
Notched outermost bone of the thumb
0009611
Bilateral ptosis
Drooping of both upper eyelids
0001488
Bladder exstrophy 0002836
Brachydactyly
Short fingers or toes
0001156
Clinodactyly
Permanent curving of the finger
0030084
Deviated nasal septum
Crooked nasal septum
Crooked septum of nose
Deviated septum of nose
[ more ]
0004411
Epicanthus
Eye folds
Prominent eye folds
[ more ]
0000286
Esophageal atresia
Birth defect in which part of esophagus did not develop
0002032
Hypoplastic helices 0008589
Hypotelorism
Abnormally close eyes
Closely spaced eyes
[ more ]
0000601
Sloping forehead
Inclined forehead
Receding forehead
[ more ]
0000340
Strabismus
Cross-eyed
Squint
Squint eyes
[ more ]
0000486
Showing of 31 |
Last updated: 7/1/2020

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


Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

  • ClinicalTrials.gov lists trials that are related to Maternal hyperphenylalaninemia. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

    Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Patient Registry

  • A registry supports research by collecting of information about patients that share something in common, such as being diagnosed with Maternal hyperphenylalaninemia. The type of data collected can vary from registry to registry and is based on the goals and purpose of that registry. Some registries collect contact information while others collect more detailed medical information. Learn more about registries.

    Registries for Maternal hyperphenylalaninemia:
    NBS Connect
    PKU Patient Registry
     

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

  • 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.
  • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.

Selected Full-Text Journal Articles


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