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​Provider’s Guide to Newborn Metabolic Screening Disorders

The below tables ​outline the newborn screening information most important to Maryland providers, including the core and secondary conditions, when conditions are screened, unsatisfactory codes, and common report comments. 

​​​For more information on conditions, visit the following two websites: 

• ​​​​HRSA Newborn Screening Resources
• CDC Newborn Screening Resources for Families​
  

​Core Conditions

Core Conditions	Primary Marker	Time Critical Condition
Propionic Acidemia (PA)	C3	Yes
Methylmalonic Acidemia (methylmalonyl-CoA mutase) (MUT)	C3	Yes
Methylmalonic Acidemia (Cobalamin disorders) (MMA)	C3	​No
Isovaleric Acidemia (IVA)	C5	Yes
3-Methylcrotonyl-CoA Carboxylase Deficiency (3-MCC)	C5OH	​No
3-Hydroxy-3-Methylglutaric Aciduria (HMG)	C5OH	Yes
Holocarboxylase Synthetase Deficiency (MCD)	C5OH	Yes
Β-Ketothiolase Deficiency (BKT)	C5OH	Yes
Glutaric Acidemia Type I (GA-I)	C5DC	Yes
Cartnitine Uptake Defect/Carnitine Transport Defect (CUD)	C0	​No
Medium-chain Acyl-CoA Dehydrogenase Deficiency (MCAD)	C8	Yes
Very Long-chain Acyl-CoA Dehydrogenase Deficiency (VLCAD)	C14:1	Yes
Long-chain L3 Hydroxyacyl-CoA Dehydrogenase Deficiency (LCHAD)	C16OH	Yes
Trifunctional Protein Deficiency	C16OH	Yes
Argininosuccinic Aciduria (ASA)	High ASA	Yes
Citrullinemia, Type I (CIT)	High CIT	Yes
Branched Chain Keto-Acidosis, commonly called Maple Syrup Urine Disease (MSUD)	High LEU + VAL	Yes
Homocystinuria	High MET	​No
Classical Phenylketonuria	High PHE	​No
Tyrosinemia, Type I	Succinylacetone present	​No
Primary Congenital Hypothyroidism (CH)	T4, TSH	​No
Congenital Adrenal Hyperplasia (CAH)	Elevated 17-OHP	Yes
S,S Disease (Sickle Cell Anemia)	FS	​No
S, Beta Thalassemia	FSA	​No
S, C Disease	FSC	​No
Biotinidase Deficiency	Absent BIO	​No
Cystic Fibrosis	High IRT with two disease causing variants	​No
Classical Galactosemia	GALT/Total Galactose	Yes
Glycogen Storage Disease Type II (Pompe)	Low GAA	Yes
Severe Combined Immunodeficiencies (SCID)	TREC (# of cycles required for PDR to identify TREC)	​No
Mucopolysaccharidosis Type I (MPS-I)	Low IDUA + Positive Glysosaminoglycans	​No
Mucopolysaccharidosis Type I (MPS-II)	Low I2S + Positive Glycosaminoglycans	​No
Fabry Disease (Not on RUSP)	Low GLA	​No
Spinal Muscular Atrophy (SMA)	Absent SMN1	Yes
X-linked Adrenoleukodystrophy (X-ALD)	Elevated C26	​​No

Secondary Conditions

Secondary Conditions	Primary Marker	Time Critical Condition
Methylmalonic Acidemia with homocystinuria	C3	​No
Malonic Acidemia	C3DC	​No
Isobutrylglycinuria (IBD)	C4	​No
2-Methylbutyrylglycinuria (2MBG)	C5	​No
3-Methylglutaconic Aciduria	C5OH	​No
2-Methyl-3-hydroxybutyric aciduria	C5OH	​No
Short-chain acyl-CoA dehydrogenase deficiency (SCADD)	C4	​No
Medium/short-chain L-3-hydroxyacyl-CoA Dehydrogenase Deficiency (M/SCHAD)	C4OH	​No
Glutaric Acidemia, Type II	C4, C5	Yes
Medium-chain Ketoacyl-CoA Thiolase Deficiency	Medium chains, only 1 case reported	​No
2,4 Dienoyl-CoA Reductase Deficiency	C10:2	​No
Carnitine palmitoyltransferase type I deficiency (CPT-I)	HIGH C0	​No
Carnitine palmitoyltransferase type II deficiency (CPT-II)	C16 +/-C18:1	Yes
Carnitine acylcarnitine translocase deficiency (CACT)	C16 +/-C18:1	Yes
Argininemia	HIGH ARG	​No
Citrullinemia, Type II	HIGH CIT	​No
Hypermethioninemia	HIGH MET	​No
Benign hyperphenylalaninemia	HIGH PHE	​No
Biopterin defect in cofactor biosynthesis	HIGH PHE	​No
Biopterin defect in cofactor regeneration	HIGH PHE	​No
Tyrosinemia, Type II	HIGH TYR	​No
Tyrosinemia, Type III	HIGH TYR	​No
Alpha thalassemia	Barts	​No
Hemoglobin C	FC	​No
Variant Hemoglobin	FV	​No
Persistent fetal hemoglobin or Btta Thalassemia Major	F	​No
Sickle cell trait	FAS	​No
Galactoepimerase deficiency	WNL GALT, elevated Tgal	​No
Galactokinase deficiency	WNL GALT, elevated Tgal	​No
T-cell related lymphocyte deficiencies	TREC (# of cycles required for PCR to identify TREC)	​No​

​Newborn VS Subsequent Screening Breakdown​

Analyte	Routinely Tested on 1st sample	Routinely Tested on 2nd sample
Thyroxine (T4)	​√​	√
TSH (Confirmatory test if T4 is low)	​	​
17-o-hydroxyprogesterone (17-OPH)	√	​
Immunoreactive Trypsinogen (IRT)	√	​
Galactose-1-P uridyl transferase enzyme (GALT)	√	​
Total galactose (galactose and galactose-1-P)	√	​
Biotinidase	√	​
Hemoglobin	√	​
Acylcarnitine Profile	√	√
Amino Acid Profile	√	√
SMA	√	√
TREC	√	√
LSD	√	√

Unsatisfactory Specimen Codes

Code​	​​Meaning
​UNS 1	​Insufficient blood to run all tests
​UNS 2	​Specimen appears scratched or abraded by capillary tube or by rubbing against heel​
​UNS 3	​Specimen appears layered, clotted or oversaturated
​UNS 4	​Specimen appears streaked with blood clots
​UNS 5	​Specimen exhibits serum rings, or appears diluted, discolored or contaminated by alcohol or formula
​UNS 6	Filter paper stretched or wrinkled in blood collection process or contaminated by ink
​UNS 7	​Essential information for identification, categorization, interpretation and follow-up were not provided​
​UNS 8	​Blood spot was not dried before mailing to the lab
​UNS 9	​Unable to obtain satisfactory test result​
​UNS 10	​Specimen degradation noted; Unacceptable for some analytes​
​UNS 10	​Sample received more than 30 days after the recorded date of collectlon
​UNS 11	​​Specimen damaged or lost in transit to the lab
​UNS 12	​There was no blood in the circles
​UNS 13	​This specimen was received with no patient information​
​UNS 14	​Blood did not elute from filter paper thus preventing the reporting of accurate results
​UNS 15	​No specimen received; Parental consent refused

​Common Newborn Screening Report Comments

Unsatisfactory Results	UNS may appear in any result field. A footnote explaining why the specimen was not acceptable will be printed at the bottom of the report. Reasons include improper specimen collection technique, damage or delay in transit, errors or discrepancy in patient identification.
Insufficient Milk Feeding	IMF may appear in the result fields for amino acids and galactose. Valid results cannot be obtained unless the infant was on milk feeding for 24 hours before blood was collected. In addition, if the infant's feeding status is unknown and the date the specimen was collected is unknown, amino acids and galactose will be reported as IMF.
Invalid	INVALID may appear in the T4 and 17-OHP fields. T4 and 17-OHP are valid markers for Congenital Hypothyroidism and Congenital Adrenal Hyperplasia, respectively, in infants greater than 24 hours of age. If the specimen was collected before 24 hours of age, the results for these analytes are invalid. INVALID may appear in the IRT field. The IRT test is invalid for infants weighing <1500 g at the time the specimen is collected. INVALID may appear in the LSD field. The LSD screen is invalid for specimens collected <24 hours of age. If collected after 24 hours, the infant must weigh >2000g or be >34 weeks gestation at the time the specimen is collected, otherwise the results for these analytes are invalid.
Borderline	Borderline may appear in the result field for Acylcarnitine Profile. Borderline ACP results indicate elevations in ACP that are most likely secondary to pharmacologic effect. Borderline may appear in the result field for IRT. Borderline IRT indicates this is the baby's first elevated IRT. These results are typically not reported for follow-up until the second IRT is elevated. Borderline may appear in the result field for LSD. Borderline LSD indicates one of the enzymes is low but not in the abnormal range.
Inconclusive	Inconclusive may appear in the result field for LSD. Inconclusive LSD screen indicates more than on enzyme is reduced. Inconclusive may appear in the result field for SMA and SCID screen. Inconclusive SMA or SCID screen means there was not enough DNA present to test for these screens.
Incomplete	Incomplete may appear in the result fields for galactose, amino acids, IRT and LSD screen. Valid results cannot be obtained if necessary data is missing in order to interpret the lab results. Missing data may include date of birth, collection date, first feeding date and time, weight or gestational age.
Transfusion	TRANS will appear in the result fields for the red cell enzyme tests (GALT, Biotinidase) and hemoglobin if the baby was transfused within 4 months of blood collection date. If these tests are performed within 4 months of a transfusion, the results will represent the status of the donor blood, not the baby's blood. If a report for a PREVIOUS sample collected BEFORE transfusion also appears below the CURRENT report, and the results are Normal as defined on page 1 of this document, a retest at 4 months of age is not required. If no sample was collected before transfusion, a specimen collected 4 months after the last transfusion is required to test the baby for galactosemia, Biotinidase deficiency and hemoglobinopathies.

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