Maternal hyperphenylalaninemia

Other Names: Maternal phenylketonuria; MPKU; Hyperphenylalaninemic embryopathy; Maternal PKU; Phenylketonuric embryopathy 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 nonphenyl ketonuric 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.

Cause

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).

Inheritance

Autosomal recessive inheritance, a 25% chance

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

Signs and symptoms

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; ), 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 . 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.

For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. 30%-79% of people have these symptoms

• Abnormal facial shape(Unusual facial appearance)
• Coarctation of aorta(Narrowing of aorta)
• Global developmental delay
• Hypoplastic left heart(Underdeveloped left heart)
• Intellectual disability(Mental deficiency)
• Intrauterine growth retardation(Prenatal growth deficiency)
• Microcephaly(Abnormally small skull)

5%-29% of people have these symptoms

• Anteverted nares(Nasal tip, upturned)
• Double outlet right ventricle
• High palate(Elevated palate)
• Hyperactivity(More active than typical)
• Hypoplasia of the corpus callosum(Underdevelopment of part of brain called corpus callosum)
• Long philtrum
• Micrognathia(Little lower jaw)
• Seizure
• Tetralogy of Fallot
• Ventricular septal defect(Hole in heart wall separating two lower heart chambers)
• Wide nasal bridge(Broad nasal bridge)

Diagnosis

Plasma amino acid concentrations were measured by standard ion exchange chromatography procedures using a Beckman 6300, Biochrom 20+, or Biochrom 30 amino acid analyzer

(i) classical phenylketonuria (CP), plasma Phe concentration ≥ 1,200 μmol/L; (ii) variant phenylketonuria (VP), plasma Phe concentration between 400–1,199 μmol/L; and (iii) benign HPA (BH), plasma Phe concentration < 400 μmol/L. The plasma Phe concentration in HPA conditions is considered optimal when in the range of 120–360μmol/L.

Treatment

In conclusion, instituting and maintaining weekly visits to a nutritionist who is experienced in treating MHPA to reinforce and make changes in the diet during pregnancy appears to be a key factor in improving plasma Phe concentrations.

NIH genetic and rare disease info

• NIH info on Maternal hyperphenylalaninemia

Maternal hyperphenylalaninemia is a rare disease.

Maternal hyperphenylalaninemia Resources
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