PhenylketonuriaPhenylketonuriaAn autosomal recessive genetic disorder characterized by a deficiency in the enzyme phenylalanine hydroxylase (PAH). Thi i t t b li This enzyme is necessary to metabolize the amino acid phenylalanine to the amino acid tyrosine. When PAH is deficient, phenylalanine accumulates and is converted p yinto phenylpyruvate which is detected in the urine. This condition can cause problems leading to progressive mental retardation and seizures However PKU retardation and seizures. However, PKU can be controlled by a diet low in phenylalanine and high in tyrosine can be a very effective treatment. So early detection is crucial”……..

Dr. Robert Guthrie is givengmuch of the credit forpioneering the earliestscreening for phenylketonuriascreening for phenylketonuriain the late 1960s using bloodsamples on filter paper

NOW It’ N t J t PKU!NOW: It’s Not Just PKU!The current newborn screening panel tests for more The current newborn screening panel tests for more than 50 disorders including hearing screening

About one in every 250 babies has one of About one in every 250 babies has one of the diseases screened for at birth

Purpose of Newborn ScreeningQuick identification of newborns with rare, serious, but treatable disordersdisorders

Early diagnosis and treatment of y gaffected infants resulting in normal growth and development

Reduction of significant human and financial costs for families and society

If treated, infants may live relatively normal lives

What is Newborn Screening?

Newborn screening on 48 disorders

12 Amino acid disorders including PKU

13 Fatty acid oxidation disorders 15 Organic acid disorders 2 Enzyme Disorders 4 Hemoglobinopathies4 g p 2 Endocrine disorders 

Organic Acid Metabolism DisordersOrganic Acid Metabolism Disorders Methylmalonic acidemia (mutase deficiency) (MUT) 2‐Methyl butyryl‐CoA dehydrogenase deficiency (2MBG)y y y y g y ( ) 3‐Methylcrotonyl‐CoA carboxylase deficiency (3MCC) Isobutyryl‐CoA dehydrogenase deficiency (IBG) 2 Methyl 3 hydroxy butyric aciduria (2M3HBA) 2‐Methyl 3 hydroxy butyric aciduria (2M3HBA) Multiple carboxylase deficiency (MCD) 3‐Methylglutaconic aciduria (3MGA) 3‐OH 3‐CH3 glutaric aciduria (HMG) Beta‐ketothiolase deficiency (BKT) Methylmalonic acidemia (Cbl A,B)y ( , ) Methylmalonic acidemia (Cbl C,D) Glutaric acidemia type I (GA I) Malonic acidemia (MAL) Malonic acidemia (MAL) Isovaleric acidemia (IVA) Propionic acidemia (PA)

F A id O id i Di dFatty Acid Oxidation Disorders Med./short‐chain L‐3‐OH acyl‐CoA dehydrogenase deficiency (M/SCHAD) Long‐chain L‐3‐OH acyl‐CoA dehydrogenase deficiency (LCHAD) Very long‐chain acyl‐CoA dehydrogenase deficiency (VLCAD) Med.‐chain acyl‐CoA dehydrogenase deficiency (MCAD)y y g y ( ) Short‐chain acyl‐CoA dehydrogenase deficiency (SCAD) Med.‐chain ketoacyl‐CoA thiolase deficiency (MCKAT) Carnitine: acylcarnitine translocase deficiency (CACT) Carnitine: acylcarnitine translocase deficiency (CACT) Carnitine palmitoyltransferase IA def. (liver) (CPT IA) Carnitine palmitoyltransferase II deficiency (CPT II) Dienoyl‐CoA reductase deficiency (DE RED) Trifunctional protein deficiency (TFP) Glutaric acidemia type II (GA II)yp ( ) Carnitine uptake defect (CUD)

i id b li i dAmino Acid Metabolism  Disorders Defects of biopterin cofactor regeneration (BIOPT(Reg))p g ( ( g)) Biopterin cofactor biosynthesis (BIOPT (BS)) Benign hyperphenylalaninemia (H‐PHE) Argininosuccinic acidemia (ASA) Argininosuccinic acidemia (ASA) Maple Syrup Disease (MSUD) Citrullinemia Type II (CIT II)

h ( ) Hypermethioninemia (MET) Tyrosinemia Type I (TYR I) Phenylketonuria (PKU)y ( ) Homocystinuria (HCY) Citrullinemia (CIT) Argininemia (ARG) Argininemia (ARG)

Other Diseases Endocrine Disorders: Congenital Adrenal Hyperplasia (CAH)(CAH)

Congenital Hypothyroidism (CH)

Enzyme Disorders: Galactosemia (GALT) Biotinidase Deficiency (BIOT)Biotinidase Deficiency (BIOT)

Hemoglobinopathies: Sickle cell anemia (Hb SS) Sickle cell anemia (Hb SS)Hb S/C Disease (Hb S/C)Hb S/Beta‐thalassemia (Hb

S/Beta‐Th)S/Beta Th) Variant Hb‐pathies (Var Hb)

J T M E h i OJust To More Emphasize On

The Direct Role Of

Newborn Screening In

Translating Preclinical

Science To Clinical Side Of

Therapy:

Congenital Adrenal HyperplasiaCongenital Adrenal Hyperplasia (CAH)

A l i  di dAutosomal recessive disorderDecrease or absence of certain adrenalhhormones• Untreated:

 S   i i t i  f l• Sex misassignment in females• Adrenal Crisis• Death• Death

• Treatment (Lifelong):• Hormone replacement therapy• Hormone replacement therapy

Congenital Hypothyroidism (CH)Congenital Hypothyroidism (CH)Approximately 10% are genetically inherited I d t     b t  d ti   f th id• Inadequate or absent production of thyroidHormone

• Untreated:• Mental retardation• Poor growth and development

 T t t (Lif l )• Treatment (Lifelong):• Daily oral thyroid replacement

G l i (GAL)Galactosemia (GAL)• Autosomal recessive disorder• Failure to metabolize the milk sugar galactose• Untreated:

• Cataracts• Cirrhosis of the liver• Mental retardation• Death

• Treatment (Lifelong):• Exclusion of galactose from the diet

Biotinidase Deficiency (BIO)Biotinidase Deficiency (BIO)• Autosomal recessive disorder• The enzyme is missing or not functioningy g gproperly• Untreated:

•Seizures•Seizures•Hearing loss•Neurological impairment•Death

• Treatment (Lifelong):•Daily oral biotin supplementsy pp

HemoglobinopathiesHemoglobinopathies(Sickle Cell Disease)

• Autosomal recessive disorder• Blood vessels become “clogged”• Untreated:

• Severe pain• Sickle cell crisis• Death from pneumococcal sepsis

• Treatment:• Penicillin prophylaxis until at leasti     f six years of age

Hearing TestHearing Test 

l O iPulse Oximeter test for heart defectsfor heart defects

best languages for translating research to

medical applicationThe best part of newborn screening is how simple it

is. The blood spots could be used for life-saving research Blood spots left over from the newborn research. Blood spots left over from the newborn

screening process hold the promise of a healthy life for all babies through research for new disease tests and

improvements in testing procedures.

THE END