Summary of Disorders Included on Louisiana’s Required Newborn Heel Stick Screening Panel State Mandates: R.S. 40:1299 et seq and LAC 48: V. 6303

Disorder Incidence Defect Clinical Symptoms Goal Metabolic Disorders Disorders of Amino Acid Metabolism Citrullinemia (CIT) 1:70,000 Deficiency of Poor appetite, irritability, Severe form: arginigosuccinic acid heavy or rapid breathing, immediately on synthase, a urea cycle lethargy, vomiting, recognition of enzyme, leads to disorientation, somnolence, hyerammonia accumulation of citrulline combativeness, coma, Milder forms: and hyperammonemia cerebral edema day 7 Homocystinuria (HCY) 1:344,000 Deficiency of cystathionine Most newborns have none. Identification and synthase leads to Development delay, mental treatment/special accumulation of retardation, psychiatric diet by day 14 homocysteine in the serum disturbances, seizures, and increased excretion in marfanoid stature and the urine ectopia lentis may develop Maple Syrup Urine Disease Decreased activity of Maple syrup odor in Severe form: (MSUD) the branched-chain alpha cerumen and urine, Immediatley ketoacid dehydrogenase irritability, poor feeding, upon recognition of complex (BCKAD) which is lethargy, intermittent metabolic acidosis; involved in degradation of apnea, opisthotonus, Milder forms: branched-chain amino acids stereotyped movements, Day 7. (leucine, isoleucine, and coma and respiratory valine) failure Phenylketonuria (PKU) LA 1:16,000 Enzyme defect in Mental retardation, Identification and phenylalanine hydroxylase seizures treatment, special results in increased diet by 10-14 days phenylalanine in blood and increased phenylketones in urine Tyrosinemia I and 1:100,000 Hepatic Type I Usually Upon confirmation II(TYR) fumarylacetoacetate asymptomatic in the of disorder. hydrolase (I) neonate. If untreated it Treatment < Hepatic cystosolic tyrosine will cause liver disease and 1 month aminotranferase cirrhosis early in infancy Type II asymptomatic in the neonate but will cause hyperkeratosis of the skin, corneal ulcers, and in some cases, mental retardation Disorders of Fatty Acid Metabolism Carnitine Acylcarnitine 1:350,000 Acylcarnitines cannot be Marked hypoglycemia, Upon recognition of translocase deficiency transported into the metabolic acidosis, cardiac disorder. Avoid (CACT)/Carnitine mitochondria for fatty acid arrythmias, and facial fasting. Palmitorytransferase oxidation thereby limiting dysmorphism Age appropriate Deficiency I and II (CPT Energy production. Heart diet. I and II) and skeletal muscle primarily affected. Carnitine Uptake Unknown Reduced carnitine limits Lethargy, hypotonia, Upon recognition of Deficiency (CUD) acylcarnitine formation hepatomegaly, and cardiac disorder. Avoid preventing transport of decompensation due to fasting. fatty acids into cardiomyopathy. Age appropriate mitochondria thereby Hypoglycemia is typical in diet. limiting energy production. acute episodes Heart and skeletal muscle particularly affected Long-Chain Fatty Acid Unknown Long-chain 3-hydroxyacyl- Occurs during prolonged Upon recognition of Deficiency (LCHAD CoA dehydrogenase fasting and/or periods of disorder. Avoid deficiency results in increased energy demands fasting. inability to metabolize long- (fever, stress). Age appropriate chain fatty acids with Hypoglycemia, elevated diet. resulting hypoglycemic liver transaminases, episodes in times of stress bilirubin, lactate, ammonia, and creatine phosphokinase (CPK) Medium Chain Acyl CoA 1:20,000 Deficiency of medium Ccain None at birth, but Upon recognition of Dehydrogenase (MCAD) acyl-CoA dehydrogenase preprandial irritability, disorder. Avoid results in inability to lethargy, jitteriness, fasting. Age metabolize medium- chain sweating, and seizures may appropriate diet. fatty acids with resulting occur as intervals between hypoglycemic episodes in feedings increase times of stress Trifunctional protein Unknown Deficiency of enzyme Onset of mitochondrial Upon recognition of Deficiency comples known as trifunctional protein disorder, avoid mitochondrial trifunctional deficiency may begin during fasting. Age protein. Long chain fatty infancy or later in life. In appropriate diet acids from food and body infancy signs and symptoms fat cannot be metabolized, include feeding difficulties, processed, and converted to lethargy, hypoglycemia, energy resulting in lethargy hypotonia and liver and hypoglycemia problems and may be at risk for heart and breathing problems, coma and sudden unexpected death. After infancy syptoms include hypotonia, muscle pain, breakdown of muscle tissue and peripheral neuropathy. Very Long Chain Acyl-CoA 1:240,000 Deficiency of very long- Presents acutel in the Upon recognition of Dehydrogenase Deficiency chain acyl-CoA neonate and is associated disorder, Avoid (VLCAD) dehydrogenase with high mortality unless fasting. Age results in inability to treated promptly; milder appropriate diet. metabolize long-chain fatty variants exist. acids with resulting Hepatomegaly, hypoglycemic episodes in cardiomyopthy and times of stress arrthymias, lethargy, hypoketotic hypoglycemia, and failure to thrive Disorders of Ogranic Acid Metabolism Beta-Ketothiolase 1:460,000 Defect in enzyme Hypoglycemia, ketonuria, Upon recognition of Deficiency (BKD) Mitochondrial acetoacetyl- metabolic acidosos disorder. Avoid CoA thiolase fasting. Age appropriate diet. Glutaric Acidemia I (GA 1) 1:92,000 Defect of Glutaryl-CoA Macrocephalic but Identification on dehydrogenase , a otherwise asymptomatic. NBS and into mitochondrial flavin- Later signs include treatment by day 7. dependent enzyme required metabolic ketoacidosis, for catabolism of essential failure to thrive, and lysine and tryptophan. sudden onset of dystonia and athetosis Isovaleric Acidemia (IVA) 1/92,000 Disorder of essential leucine Presents with metabolic Recognition of breakdown caused by a ketoacidosis, a “sweaty Hyperammonemia, defect of Isovaleryl-CoA feet” odor, dehydration , metabolic acidosis. dehydrogenase hyperammonia, ketonuria, In treatment by 7- vomiting, hypoglycemia, and 10. failure to thrive. Milder variants without neonatal illness exist. Malonic Aciduria Rare 20 cases Deficiency of malonyl-CoA May present acutely in Upon recognition of decarboxylase. Disease of neonate. Can include disorder. Avoid ketone metabolism and fatty hypoglycemia, lactic fasting. Age acid oxidation acidosis, and marked appropriate diet. lethargy. More commonly, presents during infancy or later childhood with developmental delay, seizures, vomiting, failure to thrive, hypotonia, hypoglycemia, metabolic acidosis, and cardiomyopathy. Methylmalonic Acidemia 1:46,000 MMA results from a defet Present in the meonate Recognition of (MMA), Proprionic in methylmalonyl-CoA with metabolic Hyperammonemia, Acidemia (PA), Multiple mutase which converts ketoacidosis, dehydration, metabolic acidosis. CoA Carboxylase methylmalonyl-CoA to hyperammonemia, In treatment by 7- Deficiency (MCD) succinyl-CoA or from lack of ketonuria, vomiting, 10 days

the required B12 cofactor hypoglycemia, and failture for methylmalonyl-CoA to thrive mutase (cobalamin A, B, C, D, and F). PA is caused by a defect in propionyl-CoA carboxylase which converts propionyl-CoA to methylmalonyl-CoA; Proprionic Acidemia

(See Above) 3-Methylcrotonyl-CoA 1:50,000 Enzyme defect in 3- Neonate is usually Upon recognition of Carboxylase Deficiency methylcrotonyl-CoA asymptomatic. Episodic hyperammonia, carboxylase in infant or hypoglycemia, lethargy, metabolic acidosis. mother. hypotonia, and mild In treatment by 7- developmental delay can 10 days. occur at any time from the neonatal period through childhood Enzyme Deficiencies Biotinidase 1:70,000 Defect in Biotin utilization. Hypotonia, lethargy, Identification and (Biotin is a water soluble seizures, hearing loss, treatment/suppleme vitamin.) developmental delays, optic ntation with Biotin nerve atrophy by 10-14 days Galactosemia 1:60,000 Enzyme defect with Classical: Sudden death Identification and resulting elevation of (E.coli sepsis), jaundice/ treatment/special galactose and galactose hepatomegaly, academia, diet by day 5 metabolites. cataracts, mental retardation Variants: milder symptoms Endocrine Disorders Congenital Hypothyroidism LA 1:6,250 Insufficient production of Most newborns have none. Identification and US 1:3,600-1:5,000 thyroxine due to absent, Jaundice, constipation, treatment by day 28 dysfunctional, or ectopic coarse facies/tongue, thyroid gland (primary CH) delayed skeletal maturity, or to defective Thyroid posterior fontanelle, Stimulating Hormone by the bradycardia, hypothermia, pituitary (secondary CH) mental retardation Congenital Adrenal 1:10,000 – 18,000 Deficiency of 21- Ambiguous genitalia in Identification Hyperplasia hydroxylase production by females; salt-wasting, within 30 days and the adrenal gland shock & possibly death hormone replacement Hemoglobinopathies Hemoglobinopathies 1:385 African Presence of hemoglobin S in Sickle Cell Disease Identification and American births combination with another associated with sepsis, pain treatment by 1½ to abnormal hemoglobin or beta crises, pneumonia, anemia, 2 months thalassemia gallstone, splenic enlargement Pulmonary/Digestive Disorders

Cystic Fibrosis 1:31,000 Caused by a mutation in the Chronic respiratory Identification and cystic fibrosis problems; pancreatic treatment within 2 transmembrane conductance insufficiency; male months regulator reproductive issues