newborn screening kuwait

Newborn Screening: Kuwait’s Expanded Screening

Program

Prepared by: Dr . Amir Abdelazim Ahmed clinical pathology specialist at Kuwait medical Genetic Center

Newborn Screening – What’s new? Previously:

◦ PKU, congenital hypothyroidism

At 31 October 2014 : ◦ Progressive expansion to 22 primary disorders

◦ NBS includes metabolic and endocrine conditions

Expanded NBS – 22 conditions

18 inborn errors of metabolism

2 endocrine disorders ◦ Congenital hypothyroidism

◦ Congenital adrenal hyperplasia

2 other metabolic disorders ◦ Galactosemia

◦ Biotinidase deficiency

Benefits of NBS

Identification

Early intervention

Reduced morbidity & mortality

Family planning

Risks of NBS

Parental anxiety (false positives)

Missed diagnosis (false negatives)

The right ‘not to know’

Unanticipated outcomes

Labelling – diagnosis of benign conditions

NBS: how & where is it done?

Method: Heel prick

Sample collection: newborn screening card collected by staff of each hospital

Testing Location: Newborn Screening laboratory at KMGC

Transportation: NBS cards are sent from all hospitals via special drivers

Timing of Testing Acceptable samples

◦ between 1 day (24 hours) and 7 days after birth

Best time for sample: ◦ between 2 days (48 hours) and 3 days (72 hours) after birth

If tested before 1 day (24 hours) of age,

REPEAT the test within 5 days If the baby is >5 days, screening is still

available ◦ Show Kuwait NS-protocol for details

Special Considerations Prematurity If <33 weeks - collect three specimens at 2,14and 30 days old

◦ Indicate this on NBS card (1st , 2nd , 3rd ) ◦ Premature may have false positive test results

Total Parenteral Nutrition (TPN) ◦ Certain amino acids and organic acids will be elevated ◦ Indicate this on NBS card

Transfusion ◦ Disorders may be missed ◦ Ideally complete card and obtain sample before transfusion

Early discharge ◦ If prior to 24 hours, parents should be informed that a

repeat sample must be done and hospital give him referral for 2nd sample time

The Heel Test

Sample qualitative

validity

NBS Report

Screen Positive Results

Screen positive means: ◦ Further testing is required to confirm the diagnosis

◦ Does NOT mean that the infant is affected

NSO will immediately notify parents and arrange confirmatory testing

If diagnosis is confirmed, cases refere to specialist for treatment & follow up

Report will be mailed to NSO at hospital according to the parent address , provided that correct information is completed on the screening card.

Results of Expanded NBS by MS/MS Schulze et al. Pediatrics 2003

250,000 neonates screened for 23 inborn errors of metabolism ◦ 106 newborns with confirmed metabolic disorder

70 required treatment

◦ Overall prevalence of metabolic disorder = 1/2400 ◦ 825 false positives (0.33% false positive rate) ◦ Overall specificity = 99.67% (PPV = 11.3%) ◦ Overall sensitivity = 100% for classic forms of disorders

= 92.6% for variants

◦ 61 /106 were judged to have benefited from screening and treatment 58% of true positives

1/4100 newborns

Negative Results

Results will go to: ◦ Submitting health care professional/hospital

If you suspect that an infant or child has symptoms of a screened condition and their NBS results are negative – please refer to the appropriate specialist for evaluation

◦ NBS panel does not screen for every metabolic condition

◦ NBS is a screening test – not diagnostic


18 inborn errors of metabolism ◦ 7 organic acid disorders

◦ 5 fatty acid oxidation disorders

◦ 6 amino acid disorders

2 endocrine disorders

2 other metabolic disorders

Inborn errors of metabolism

Rare

Usually autosomal recessive inheritance

◦consanguinity is more common Symptoms secondary to a problem in the

metabolic pathway

Usually not significant dysmorphism

Early recognition and intervention can be lifesaving

Organic Acid Disorders

Isovaleric acidemia (IVA) Glutaric acidemia type 1 (GA1) Multiple carboxylase deficiency (MCD) Methylmalonic acidemia (MMA) 3-methylcrotonyl-CoA carboxylase (3MCC)

deficiency Propionic acidemia (PA) Β-ketothiolase deficiency (BKT)

Organic Acid Disorders

What are organic acid disorders? ◦ Body cannot metabolize certain amino acids and fats ◦ Accumulation of organic acids in blood and urine ◦ Serious potentially preventable effects on health and

development, including death

Symptoms ◦ acute encephalopathy, vomiting, metabolic acidosis,

ketosis, hyperammonemia, hypoglycemia, coma ◦ dehydration, failure to thrive, hypotonia, global

developmental delay ◦ sepsis, death

Treatment ◦ Low protein diet / restrict amino acids, ◦ Supplements: carnitine, biotin, riboflavin, glycine ◦ Avoid fasting

Fatty Acid Oxidation Disorders

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency

Very long-chain acyl-CoA dehydrogenase deficiency (VLCAD)

Long-chain L-3-OH acyl-CoA dehydrogenase deficiency (LCHAD)

Trifunctional protein deficiency (TFP) ◦ catalyzes 3 steps in mitochondrial beta-oxidation of fatty acids

3-Hydroxy-3-methylglutaryl-CoA lyase def.(3HMG)

Disorders of Fatty Acid Oxidation

What are disorders of fatty acid oxidation? ◦ Breakdown of fatty acids in mitochondria is an essential

part of body’s ability to produce energy

◦ Disorder: inability to break down fatty acids

Symptoms ◦ Decompensate with any catabolic stress

fever, fasting, intercurrent illness

◦ Hypoketotic hypoglycemia, liver, muscle, heart disease

◦ Lethargy, seizures, coma, sudden death (SIDS)

Treatment ◦ Avoid fasting

◦ IV glucose when ill to prevent hypoglycemia

◦ Frequent feeding

Amino Acid Disorders

Phenylketonuria (PKU) Maple syrup urine disease (MSUD)

Tyrosinemia type 1 (TYR 1) ◦Common in French Canadians

Homocystinuria (HCY) Citrullinemia (CIT) Argininosuccinic acidemia (ASA)

Amino Acid Disorders

What are amino acid disorders? ◦ Occur when the body cannot either metabolize or

produce certain amino acids

◦ Result in toxic accumulation of substances

◦ Serious potentially preventable effects on health and development including death

Symptoms (untreated) example PKU ◦ Hyperphenylalaninemia (neurotoxic)

◦ Microcephaly, epilepsy, mental retardation, behaviour problems

Treatment ◦ Diet: reduce phenylalanine, low protein, supplement

cofactors or essential amino acids

Endocrine Disorders: CH

Congenital Hypothyroidism (CH)

What is CH? ◦ inadequate thyroid hormone production

◦ Anatomic defect in gland, dyshormogenesis, iodine deficiency

Symptoms ◦ MR, ↓ growth & bone maturation, neurologic problems:

spasticity, gait abn, dysarthria, autistic behaviour

Treatment ◦ Diagnosis made before 13 days to prevent symptoms

◦ Thyroid hormone replacement

Endocrine Disorders: CAH

Congenital Adrenal Hyperplasia (CAH)

What is CAH?

◦ Impaired synthesis of cortisol by the adrenal cortex leads to ↑↑↑ androgen biosynthesis

◦ Inability to maintain adequate energy & blood glucose level to meet stress of injury & illness

Symptoms

◦ Virilization (♀ ambiguous genitalia), precocious puberty, infertility, short stature

◦ Renal salt wasting leads to FTT, vomiting, dehydration, hypotension, hyponatremia, & hyperkalemia

Treatment

◦ Glucocorticoid replacement therapy

Other Disorders: Biotinidase deficiency

What is biotinidase deficiency? ◦ Biotinidase is responsible for recycling biotin – a cofactor for

4 dependant carboxylases

Symptoms ◦ Metabolic ketoacidosis, organic aciduria, mild

hyperammonemia

◦ Seizures, hypotonia, ataxia, developmental delay, vision problems, hearing loss, cutaneous abnormalities

Treatment ◦ 5-10mg of oral biotin per day, long term treatment prevents

all symptoms

Other Disorders: Galactosemia

What is galactosemia? ◦ Lactose is main sugar in breast milk & infant formulas

◦ Metabolized into glucose and galactose in the intestine

◦ Unable to break down galactose

Symptoms ◦ Feeding problems, FTT, bleeding, infection, liver failure,

cataracts, mental retardation, death

Treatment ◦ Lactose-galactose-restricted diet

must be started in first 10 days of life to prevent symptoms

◦ Even with treatment - ↑ developmental delay, speech problems, abn motor function, premature ovarian failure

References Ontario newborn screening guideline protocol National Newborn Screening & Global Resource Center http://genes-r-us.uthscsa.edu/

newborn screening kuwait

Health & Medicine