Newborn Screening For Genetic Disorders

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Prepared by Hamad ALAssaf

Alassaf_h@yahoo.com

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Introduction

• Newborn screening is the practice of testing all babies for certain disorders and conditions that can hinder their normal development.

• Early detection and treatment can help prevent intellectual and physical disabilities and life-threatening illnesses.

• Many infants are asymptomatic

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Newborn Screening Program Criteria

1- The disease should not be clinically apparent at the time of screening

2- The disease should have a relatively high incidence in the population screened.

3- The disease should be treatable & so results of screening test must be obtained before irreversible damage is likely to have occurred.

4- Screening test should be simple & reliable. 3

Examples of screening programs

Metabolic Disorders Amino Acid Disorders

- Phenylketonuria (PKU) Carbohydrate Disorders - Galactosemia

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Hemoglobin Disorders -Sickle Cell Disease Endocrine Disorders -Congenital hypothyroidism Other Disorders - Cystic fibrosis

Phenylketonuria (PKU)

- Autosomal Recessive Inheritance (Chromosome 12). - Prevalence : 1 in 10,000 ( in USA) - Caused by a lack of the enzyme phenylalanine hydroxylase. - Causing an increase in the substrate phenylalanine and a decrease in the product tyrosine.

Clinical Features of untreated PKU -Severe mental retardation – Microcephaly - Seizures -Decrease Pigmentation of skin

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- Can be avoided by restricting the intake of phenylalanine in the diet and add tyrosine. - Pregnant women with PKU must be on phy- free diet or newborns will be mentally retarded at birth

PKU

• PKU Screening program for neonate (6 –14 days of life) using

Guthrie test • Test has to be confirmed by

measuring blood phenylalanine

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Galactosemia • Autosomal Recessive Inheritance • Prevalence : 1 in 60,000 (in USA) • Caused by an inherited lack of the GALT enzyme • Leading to accumulation of galactose – 1- phosphate

Clinical Features: • Mental Retardation - Liver diseases (cirrhosis, Jaundice) - Hypoglycemia - Cataracts (osmotic damage) - Avoid dairy Products (galactose from lactose) at least the first 2 years of life.

-Diagnosis of Galactosemia can be suspected from demonstration in the urine of a reducing sugar other than glucose. - Galactilol level amniotic fluid (Antenatal Diagnosis) 7

Sickle Cell Disease

• Autosomal Recessive Inheritance • Prevalence : 1 in 500 (U.S. African American). • A missense mutation occurs when adenine replaces thymidine.

• Causing valine to replace glutamic acid in the sixth position of the β-globin chain. • RBCs spontaneously sickle in the peripheral blood if the amount of sickle hemoglobin is

greater than 60%.

Clinical Features:

- Anemia - Painful Crises - Sepsis - Stroke * Diagnosis by Blood Sickling Solubility Test

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Congenital hypothyroidism

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Congenital hypothyroidism

• is a condition of thyroid hormone deficiency present at birth. • Prevalence: 1 in 4000 newborn (USA). • If untreated for several months after birth, severe congenital

hypothyroidism can lead to growth failure and permanent intellectual disability.

• Screening is done by measuring thyroxin (T4), thyrotropin (TSH) (first weeks of life).

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Cystic Fibrosis

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Cystic Fibrosis

• Autosomal Recessive Inheritance (chromosome 7) • Prevalence: 1 in 3200 (U.S. Caucasian) • Caused by mutations in the CFTR gene encoding the CF transmembrane

regulator.

Clinical Complications:

- Cardiopulmonary Complications (most common cause of death). - Pancreatic insufficiency - Infertility (congenital bilateral absence of vas deferens) - Liver disease (cirrhosis)

Screening by measuring immunoreactive trypsinogen (IRT) in dried blood spots. 12

References

• Robbins BASIC PATHOLOGY (9th edition) (KUMAR, ABBAS, ASTER).

• Rapid Review PATHOLOGY (3rd edition) (Edward F. Goljan)

• Medical Embryology (11th edition) (T.W. Sadler).

• Tietz Textbook of Clinical Chemistry and Molecular Diagnostics (5th edition) - Carl A. Burtis; Edward R. Ashwood; David E. Bruns

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