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Disease Profile

Maternal hyperphenylalaninemia

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

Neonatal

ICD-10

E70.1

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)

Maternal phenylketonuria; MPKU; Hyperphenylalaninemic embryopathy;

Categories

Congenital and Genetic Diseases; Ear, Nose, and Throat Diseases; Metabolic disorders;

Summary

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.

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
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

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

  • 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