Early Dietary Treated Patients With Phenylketonuria Can Achieve Normal Growth and Mental Development.

March 19, 2020 updated by: Monica Ibrahim, Assiut University
The study aim is to follow up body growth(body weight by kg, length by cm, head circumference, abdominal circumference, and body mass index ) and mental development of infants on phenylalanine restricted diet in comparison with normal matchable infants.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Phenylketonuria is rare genetic disease caused by mutation in gene of phenylalanine (Phe) hydroxylase that converts Phenylalanine into tyrosine. The absence of this enzyme leads to elevation and accumulation of Phenylalanine and, increased phenylketones in urine (hence PKU), and also leads to decrease myelin formation, dopamine, norepinephrine, and serotonin production.

Phenylketonuria worldwide affects about 1 in 12,000 babies.

In Egypt the incidence rate reported 1 : 3000 (0.03%), The actual prevalence of PKU in this study were 1/3000. This is higher than that reported by Temtamy25, who found in a pilot study on 15,000 newborns in 3 governorates in Egypt that the incidence of PKU was 1/ 7500 . The latest consensus in Egypt showed that at least one million babies are born every year.

Phenylalanine hydroxylase deficiency (PAH deficiency) causes a spectrum of disorders, including classic phenylketonuria (PKU).

A rarer form of hyperphenylalaninemia is tetrahydrobiopterin deficiency, which occurs when the PAH enzyme is normal, and a defect is found in the biosynthesis or recycling of the cofactor tetrahydrobiopterin (BH4).

Elevations of phenylalanine in the plasma depend on the degree of enzyme deficiency. In patients with severe PAH deficiency (previously referred to classic phenylketonuria ), plasma phenylalanine levels on unrestricted diet usually exceed 20 mg/dL (>1,200 μmol/L). In affected infants with plasma concentrations >20 mg/dL, excess phenylalanine is metabolized to phenylketones (phenylpyruvate and phenylacetate) that are excreted in the urine, giving rise to the term phenylketonuria (PKU).

If left untreated and not detected early , irreversible damage may occur due to the accumulation of Phenylalanine and its metabolites in the body and will affect the growth and development of patients .

Without treatment most children develop profound and irreversible intellectual disability, seizures, hyperactive behavior with autistic features, psychiatric symptoms, eczema, musty body odor, and light pigmentation.

Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by heel prick, typically performed 2-7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding. PKU is commonly included in the newborn screening panel of many countries and Egypt , with varied detection techniques. Most babies are screened for PKU soon after birth.

If left untreated and not detected early , irreversible damage may occur due to the accumulation of Phenylalanine and its metabolites in the body and will affect the growth and development of patients .

Without treatment most children develop profound and irreversible intellectual disability, seizures, hyperactive behavior with autistic features, psychiatric symptoms, eczema, musty body odor and light pigmentation.

Newborn screening is performed to detect the disease and initiate treatment before any damage is done. The blood sample is usually taken by heel prick, typically performed 2-7 days after birth. This test can reveal elevated phenylalanine levels after one or two days of normal infant feeding. PKU is commonly included in the newborn screening panel of many countries and Egypt , with varied detection techniques. Most babies are screened for PKU soon after birth.

Treatment is with a diet low in foods that contain phenylalanine and special supplements. Babies should use a special formula with a small amount of breast milk. The diet should begin as soon as possible after birth and be continued for life. People who are diagnosed early and maintain a strict diet can have normal health and a normal life .

The target of the treatment is to reach optimal health ranges of phenylalanine (or "target ranges") are between 120 and 360 µmol/L or equivalently 2 to 6 mg/dL, and aimed to be achieved during at least the first 10 years, to allow the brain to develop normally.

The dietary restriction in phenylketonuria should be only in protein diet (phenylalanine),while fat and carbohydrate diet don't need to be restricted.

Lifelong treatment will provide the best effect on growth and development, prevents neurocognitive impairment and abnormal executive functioning and helps maintaining mental health.

Anthropometric measures are important for evaluating the growth development and nutritional status of infants with phenylketonuria.

The dietary restriction in phenylketonuria should be only in protein diet (phenylalanine),while fat and carbohydrate diet don't need to be restricted.

Lifelong treatment will provide the best effect on growth and development, prevents neurocognitive impairment and abnormal executive functioning and helps maintaining mental health.

Anthropometric measures are important for evaluating the growth development and nutritional status of infants with phenylketonuria.

Intelligence and mental development in PKU PKU results, in untreated patients, a profound intellectual disability and more subtle cognitive deficits in individuals who were treated early and continuously. The assessment of intellectual functioning in PKU has been an important target outcome variable since the implementation of neonatal PKU screening programs in the 1960s . Research on intellectual functioning in individuals with PKU has played a significant role in guiding treatment recommendations and improving outcomes.

Brumm and Grant conducted a literature review examining the relationship between intellectual outcome and treatment parameters including initiation of treatment, duration of treatment, and blood phenylalanine (Phe) levels from infancy through adulthood. While current PKU treatment practices have eliminated severe neurological and cognitive impairment, evidence suggests that intellectual functioning, although typically within the average range when PKU is treated early and continuously, may not be maximized under the current definition of well-controlled PKU, which is based on blood Phe levels.

Study Type

Observational

Enrollment (Anticipated)

50

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

  • Name: Shaimaa Khalaf
  • Phone Number: 01001400503

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 year to 1 year (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Non-Probability Sample

Study Population

Cases:Infants with hyperphenylalaninemia on special formula and diet Controls: normal healthy children match with cases in the same social class, age and sex

Description

Inclusion Criteria:

  1. Infants with hyperphenylalaninemia on special formula and diet
  2. Infants of both sexes
  3. Age since birth till three years
  4. Type of feeding : diet restriction of phenylalanine
  5. Controls: normal healthy children match with cases in the same social class, age and sex

Exclusion Criteria:

  1. Age greater than three years
  2. Patients diagnosed with PKU and not regular in feeding for special diet and formula.
  3. PKU patients not diagnosed since birth

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Case-Control
  • Time Perspectives: Cross-Sectional

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Patients with Phenylketonuria
Dietary supplement: phenylalanine restricted diet
Infants with hyperphenylalaninemia on special formula and diet
normal healthy children
Dietary supplement: phenylalanine restricted diet
Infants with hyperphenylalaninemia on special formula and diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Normal growth in early dietary treated patients with Phenylketonuria to assessed by body mass index in kg/m^2
Time Frame: one year
Normal growth in early dietary treated patients with Phenylketonuria to assessed by body mass index in kg/m^2
one year
Normal growth in Early dietary treated patients with Phenylketonuria to assessed by head circumference in centimeters
Time Frame: one year
Normal growth in Early dietary treated patients with Phenylketonuria to assessed by head circumference in centimeters
one year
Normal growth in Early dietary treated patients with Phenylketonuria to assessed by abdominal circumference in centimeters
Time Frame: one year
Normal growth in Early dietary treated patients with Phenylketonuria to assessed by abdominal circumference in centimeters
one year
Mental development in early dietary treated patients with Phenylketonuria to assessed by using Emerging Pattern Of Behavior of infants
Time Frame: one year
Mental development in early dietary treated patients with Phenylketonuria to assessed by using Emerging Pattern Of Behavior of infants
one year
Comparison between early dietary treated patients with Phenylketonuria with normal matchable infants regarding normal growth and mental development
Time Frame: one year
Comparison between early dietary treated patients with Phenylketonuria with normal matchable infants regarding normal growth and mental development
one year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Assiut University

Investigators

  • Study Director: Farouk Hassanein, Assiut University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Anticipated)

May 1, 2020

Primary Completion (Anticipated)

May 1, 2021

Study Completion (Anticipated)

October 1, 2021

Study Registration Dates

First Submitted

March 7, 2020

First Submitted That Met QC Criteria

March 7, 2020

First Posted (Actual)

March 10, 2020

Study Record Updates

Last Update Posted (Actual)

March 23, 2020

Last Update Submitted That Met QC Criteria

March 19, 2020

Last Verified

March 1, 2020

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • Phenylketonuria

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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