Metabolic disorders of proteins

Clinical Biochemistry Metabolic Disorders of Proteins

By: Amir Nader Emami Razavi


What is a metabolic disease?

“Inborn errors of metabolism”
inborn error : an inherited (i.e. genetic)
disorder
metabolism : chemical or physical changes
in a biological system

June 26, 2012 Total slide. 132 2



Garrod’s hypothesis

A B Cproduct deficiency
substrate excess
D toxic metabolite



Small molecule disease Organelle disease
Carbohydrate Lysosomes
Protein Mitochondria
Lipid Peroxisomes
Nucleic Acids Cytoplasm



How do metabolic diseases present
in the neonate ??
Acute life threatening illness
encephalopathy - lethargy, irritability, coma
vomiting
respiratory distress
Seizures, Hypertonia
Hepatomegaly (enlarged liver)
Hepatic dysfunction / jaundice
Odour, Dysmorphism, FTT (failure to thrive),
Hiccoughs



How do you recognize a metabolic
disorder ??
Index of suspicion
eg “with any full-term infant who has no antecedent
maternal fever or PROM (premature rupture of the
membranes) and who is sick enough to warrant a blood
culture, one should proceed with a few simple lab tests.
Simple laboratory tests
Glucose, Electrolytes, Gas, Ketones, BUN (blood urea
nitrogen), Creatinine
Lactate, Ammonia, Bilirubin
Amino acids, Organic acids


Inborn Errors of Metabolism
An inherited enzyme deficiency leading to the
disruption of normal bodily metabolism
Accumulation of a toxic substrate
(compound acted upon by an enzyme in a
chemical reaction)
Impaired formation of a product normally
produced by the deficient enzyme



Three Types

Type 1: Silent Disorders
Type 2: Acute Metabolic Crises
Type 3: Neurological Deterioration



Type 1: Silent Disorders

Do not manifest life-threatening crises
Untreated could lead to brain damage and
developmental disabilities
Example: PKU (Phenylketonuria)



Type 2: Acute Metabolic Crisis

Life threatening in infancy
Children are protected in utero by maternal
circulation which provide missing product
or remove toxic substance
Example OTC (Urea Cycle Disorders)



Type 3: Progressive Neurological
Deterioration
Examples: Tay Sachs disease
Gaucher disease
Metachromatic leukodystrophy
DNA analysis show: mutations



Genetic Basis
of
Inherited Disorders

Point mutations,
Insertions, Deletions,
Missense Mutations
and Rearrangements



Generalities of Inherited Disorders

Although each
individual IEM is rare,
cumulatively they occur
~ 1:5000 live births
Majority of IEM follow
an autosomal recessive
mode of inheritance



Inborn Errors of Metabolism

Uneventful delivery
Normal birth weight
Non-dysmorphic (no physical findings)
Uneventful days /weeks



Defective Proteins and Disease
Defects in Carbohydrate Metabolism
Defects in Cholesterol and Lipoprotein
Metabolism
Mucopolysaccharide and Glycolipid Disorders
Defects in Amino and Organic Acid Metabolism
Porphyrias and Bilirubinemias
Errors in Fatty Acid Metabolism
Defects in Nucleotide Metabolism
Disorders in Metal Metabolism and Transport
Defects in Peroxisomes
Diseases Associated with Defective DNA Repair


Defective Proteins and Disease

Oxygen carrying proteins
Connective tisue proteins
Clotting factors



Diseases Associated with
Oxygen Carrying Proteins

Sikle-Cell Anemia
B-Talassemia
A-Talassemia



Connective Tissue Proteins

Ehlers-Danlos Type I- Type VIII
Ehlers-Danlos with Platelet Dysfunction
Marfan's Syndrome
Cutis Laxa
Occipital Horn Syndrome Cutis Laxa, X-linked
Osteogenesis Imperfecta Type I
Osteogenesis Imperfecta Type I-C
Osteogenesis Imperfecta Silent Type II/III
Osteogenesis Imperfecta Type IV
Osteogenesis Imperfecta Neonatal Lethal form
Osteogenesis ImperfectaTotal slide. 132
June 26, 2012 progressively deforming 18


Clotting Factor Dysfunction
Afibrinogenemia complete loss of fibrinogen, Factor I
Dysfibrinogenemia dysfunctional fibrinogen, Factor I
Factor II Disorders
Factor III (tissue factor) is the only coagulation factor for which a congenital defect has not been
identified
Factor V Deficiency Labile Factor deficiency
Factor VII Deficiency
Hemophilia A Factor VIII deficiency
Hemophilia B Factor IX deficiency
Factor X Deficiency
Factor XI Deficiency Rosenthal Syndrome, Plasma Thromboplastin Antecedent (PTA) deficiency
Factor XII Deficiency Hageman factor deficiency
Factor XIII Deficiency
Factor V & VIII Combined Deficiency
Factor VIII & IX combined Deficiency
Factor IX & XI Combined Deficiency
Protein C Deficiency
Protein S Deficiency
Thrombophilia Antithrombin III deficiency
Giant Platelet Syndrome platelet glycoprotein Ib deficiency
von Willebrand Disease
Fletcher Factor Deficiency Prekallikrein deficiency


Defects in Amino Acid Metabolism

Phenylketonuria
Type I Tyrosinemia - Tyrosinosis
Type II Tyrosinnemia - Richner-Hanhart Syndrome
Type III Tyrosinemia
Alcaptonuria
Homocystinuria
Histidinemia
Maple Syrup Urine Disease, MSUD
MSUD Type Ib
MSUD Type II
Methylmalonic Aciduria
Non-ketonic Hyperglycinemia Type I (NKHI)
Hyperlysinemia


Syndrome 1



Case 1
Patrick
Birth History: Full Term, 3,620 gm
Uncomplicated Pregnancy, Labor & Delivery
Mother 24 yr old, healthy
No Prenatal exposure to alcohol, drugs,
infection, known teratogens
Discharged home on day of life 2



Case 1 (CONTINUED)
Developmental Hx Seizure History
Rolled over – 3 months First – 11 m
Social smile - 4 m Generalized, tonic/clonic
Stand alone – 14 m Total – 4 seizures
First word – 18 m MRI – decreased
grey/white differentiation
Phrases – not yet and cortical atrophy
Walk alone – 2 yr



Case 1 (Cont)

Physical Exam
Growth
Blond hair, blue eyes
Non-dysmorphic child
Neurological exam:
Decreased tone, brisk reflexes



Normal Patrick
• Abnormal high intensity signal in deep white matter
• Leucodystrophy and Cortical atrophy


Case 2
Jeremy newborn male Mother - 19 yr old
Full Term: 3,100 gm First Pregnancy
Uncomplicated P,L & D Father -18 yr old
No perinatal infection, Healthy
no alcohol, no drugs, no
known teratogens



Case 2
Physical Exam and Labs
Ht & Wt = 70% General exam normal
HC< 5% Neurological exam - normal
Urine Ferric Chloride (FeCl3) is positive



Case 2

Jeremy is now 13
years old and exhibits
Persistent
microcephaly
Spasticity
Mental retardation
Coarctation of Aorta



Case 3
Luis (8yo) referred to
Developmental
Pediatrics clinic

Chief Complaint:
Hyperactivity and
Learning Disabilities

Patient and his Brother
•Self selects diet
•low in meat, eggs, cheese
•enriched in fruits / vegetables
June 26, 2012 •Similar
Total slide. 132 pigmentation to his brother
29


Case 4
Hannah: 6 month old female
Diagnosed with metabolic
disorder on abnormal newborn
metabolic screen
Normal growth / development
Normal physical exam
On treatment with metabolic
formula



All four cases

Examples of hyperphenylalanemia
Defects in metabolism of phenylalanine
Prototype – PKU
Elevation of PHE > 20 mg/dl
Normal < 2 mg/dl



PKU
Clinical Findings
Mousy or musty odor
Exzema
Fair coloring (decreased hair and skin
pigmentation)
Behavior Problems

Mental Retardation
Lose ~ 1 IQ point per week of non-treatment



Phenylalanine Metabolism

Food Catabolism
Phenylalanine
PHE Essential AA
50% Body Protein
Major
TYR
interconversions
Melanin through tyrosine

DOPA

NE / EPI


Conditionally
Essential AA



Essential Amino Acids
Histidine
Isoleucine
Leucine
Lysine
Methionine (and/or cysteine)
Phenylalanine (and/or tyrosine)
Threonine
Tryptophan
Valine


Urine
Alternate Disposal
Phenyl lactate
Phenylacetate
Phenylethylamine
Phenylacetyl glutamine

Mousy or musty
odor


PKU
Autosomal Recessive disorder caused by
mutation in PAH gene
Newborn screening started in 1963
Incidence: 1 in 15,000
Subtypes and heterogeneity
Classic
Moderate and mild
Non-classical or non-PKU hyperphenylalaninemia



PKU
Classic
Moderate and mild
Non-classical or non-PKU hyperphenylalaninemia
 % enzyme activity determines clinical severity


PKU
Classic (tolerate < 250mg phe/day)
Mild (tolerate 400-600mg phe/day)
Hyperphenylalaninemia (normal diet)
 % enzyme activity determines clinical severity


PKU
Classic
Moderate Tetrahydrobiopterin (BH4) responsive
Mild Hyperphenylalaninemia
Hyperphe • Urine pterins
June 26, 2012 • blood dihydropteridine reductase 41
Total slide. 132


BH4 Responders
PAH mutation
62% catalytic
21% regulatory
Allelic pattern
1 mild + 1 severe
2 mild
2 severe (rare)
Diet – BH4
without protein
restriction


Biological Effects

HyperPhe inhibits transport of large, neutral AA
into the brain (as does Leucine)
Inhibition of protein and neurotransmitters
 Deficiencies of dopamine, serotonin



Major Neuropathologic changes

Hypomyelination (Phe-sensitive oligodendrocytes)
White matter degeneration (leucodystrophy)
Developmental delay/arrest cerebral cortex

Microcephaly
Mental retardation
Seizures



Non-Neuro pathology

Hypomelanosis – Why ?



Non-Neuro pathology

Hypomelanosis
Blond hair, blue eyes, pale
Deficient Tyrosine production (precursor of
Melanin)

Cardiac
Coarctation of the Aorta



Maternal PKU syndrome

First mentioned in literature in 1937
First mentioned as a complication of PKU
in 1956
Women with MR and PKU has 3 children, all
retarded despite not having PKU
Microcephaly and cardiac defects reported
in 1960’s
1983 – MPKUCS begun


Maternal PKU Collaborative Study

Untreated women
92% risk of mental retardation
73% risk of microcephaly
40% risk of low birth weight
12% risk of congenital heart disease
Reduced risk if maternal plasma phe levels are
normalized pre-conceptually



Maternal PKU syndrome

Dose-Response Relationship
Goal: Phe level between 2-6 mg/dl by 8 weeks



The longer it
takes to get Phe
level < 8 mg/dl
the lower the IQ
of the baby



Balancing Metabolic Control

Exposure to Elimination
normal of PHE
PHE intake from the diet




Exposure to normal PHE
intake:
Elevations of PHE
Elevations of PHE-ketones
Deficient TYR, DOPA,
NE, EPI
Mental retardation /
seizures




Exposure to normal PHE
intake:
Elevations of PHE
Elevations of PHE-ketones
= Bad
NE, EPI
Mental retardation /
seizures




Elimination of PHE
from the diet:
Decreases PHE
Decreases PHE-ketones
NE, EPI
DEATH from essential
AA deficiency




Elimination of PHE
from the diet:
Decreases PHE
Decreases PHE-ketones
Bad =
NE, EPI
DEATH from essential
AA deficiency



Optimal Therapy of PKU
Initiate treatment by 7 days of life
Phenylalanine levels
Age Level Freq of Testing
0-12 months 2-6 mg/dl 1x/week
1-12 years Same 2x/month
> 12 years 2-15 mg/dl 1x/month

Pregnancy 2-6 mg/dl* 2x/week
June 26, 2012 * 3m before conception
Total slide. 132 59


summery
Hyperphenylalanemia Treatment is
An abnormal lab Effective if begun
finding early and continued
Several defects may for life
result in hyperphe
Aggressive
Specific Dx is critical management
PHE restriction in during growth and
BH4 deficiency is lethal during illness



What about our cases??

Patrick – case 1 Jeremy – case 2
 Dx ?  Dx ?
3 yr old with Newborn with
developmental delay microcephaly and + FeCl3
and seizures…..
Now mentally retarded
Choices
2. Classic PKU – treated or untreated
3. Maternal PKU
4. Hyperphe


What about our cases??

Patrick – case 1 Jeremy – case 2
 Classic PKU (mod)  Maternal PKU syndrome
Newborn with
3 yr old with microcephaly and + FeCl3
developmental delay Now mentally retarded
and seizures….. He is metabolically
Patrick has permanent normal… but his mother
disabilities had PKU
His mother wants more
children but is not on diet



Our Cases
Luis - Case 3 Hannah - Case 4
Dx ?  Dx ?
8yo with learning 6 month old
disability and Normal growth and
hyperactivity development

Choices
2. Classic PKU – treated or untreated
3. Maternal PKU
4. Hyperphe


Our Cases
Luis - Case 3 Hannah - Case 4
 Classic PKU (Mexico)  Classic PKU, treated
On treatment Continues to do well
His hyperactivity has on therapy
improved Growth, development
He will not regain and intellectual
normal intellect situation are normal



Syndrome 2



Jakob

Jakob was the product of a full term
pregnancy
Appeared healthy until day of life nine
Hospitalized in ICU
At 9 months Jakob is developmentally
normal and growing well
However, some times his amino acid
levels are dramatically elevated.



MSUD

What is MSUD ?
What odor was the physician asking mom about ?
Where else can you smell it ?
Is odor a reliable physical finding ?
What causes neurotoxicity ?
What is the long-term treatment and outcome ?



MSUD

Autosomal Recessive
Mutations in branched chain α-ketoacid
dehydrogenase (BCKDH)
Mitochondrial enzyme complex
3 subunits (E1, E2, and E3) encoded by 4
unlinked genes

E1 decarboxylase – heterotetramer (α and β
subunits)
E2 transacylase
E3 dehydrogenase

 E1 is thiamine dependent


Maple Syrup Urine Disease

Classical
Normal newborn, hours to days
Poor feeding and drowsiness
metabolic acidosis, hypoglycemia, cerebral
edema, respiratory distress, hiccups, apnea,
bradycardia, hypothermia, coma



Clinical Manifestations

Time Symptom/Sign
12-24 hours Maple syrup odor to cerumen
Elevated BCAA
2-3 days Irritability, poor feeding
Ketonuria
4-5 days Encephalopathy (lethargy,
apnea, atypical movements
7-10 days Coma and respiratory failure


Metabolic Defect

BCAA amino-
transferases

BCKDH
- Rate limiting



Branch Chain Amino Acids

Leucine, Isoleucine and Valine
Comprise ~40% of essential AA
During fasting, ~ 80% of AA released is
recycled back into protein synthesis




Transamination and oxidative disposal of leucine
occurs in skeletal muscle (50%), kidney (25%) and
gut/liver (25%)
Nitrogen released is used to form glutamate -> alanine -
> glucose (alanine aminotransferase reaction)

Leucine + α-Ketoglutarate -> α-Ketoisocaproate and Glutamate
Glutamate and Pyruvate -> α-Ketoglutarate and Alanine
Alanine -> -> -> Glucose



Increase in supply from diet or proteolysis
must be met with appropriate increase in
anabolic pathway (blocked in disorder)
Most severe biochemical intoxication caused by
catabolism of endogenous protein



Defect leads to elevated levels, more
pronounced in infants and children due to
enhanced rates of growth
Leucine accumulation is most toxic



Signs/Symptoms of Acute Toxicity

Ataxia (unsteady, clumsy movements)
Acute dystonia (involuntary muscle contractions)
Mood swings
Nausea, Vomiting, and Anorexia
Hallucinations
Altered level of consciousness
Stroke, coma, and death


Signs/Symptoms of Chronic Toxicity

Mood Disorders – anxiety and depression
Mental retardation
Neurologic deficits (stroke)



Neurotoxicity of Leucine

• Leucine and KIC intracellular
accumulation results in cellular edema



Leucine and KIC intracellular accumulation
results in cellular edema
Leucine accumulation inhibits entry of other
large neutral amino acids




• Leucine and KIC
intracellular accumulation
• Leucine accumulation
inhibits entry of other large
neutral amino acids
Disrupted monoamine
transmitter production
 Decreased ‘fast’ neurotransmitter pools – glutamate,
GABA, aspartate


Leucine and KIC intracellular accumulation
Leucine accumulation inhibits entry of other
large neutral amino acids
Metabolites (KIC) induce oxidative injury
 Melatonin, Vitamins C and E may be protective



1. Excess KIC results in consumption of substrates needed
for malate-aspartate shuttle resulting in increased brain
lactate and energy failure



KIC + glutamate Leucine + α-Ketoglutarate

Increased Aspartate utilization

Decreased functioning of malate-aspartate shuttle

Decreased transfer of reducing equivalent

Energy failure And lactic acidosis




Glutamic Acid is a critical excitatory
neurotransmitter
Leucine is trafficked to the brain as a source
of –NH2 groups (Leucine-Glutamate cycle)



Elevated Leucine

Accumulation of KIC

drives leucine-glutamate cycle in reverse direction

LEU decreased brain glutamate

2-ketoisocaproate

Isovaleryl-CoA


Elevated Leucine

Altered brain water homeostasis

cell edema



Elevated Leucine

Inhibits entry into the brain of other large,
neutral AA (as in PKU) phenylalanine, tryptophane, methionine,
tyrosine,histidine, threonine, and BCAA (L1-NAA-t)

Dystonia and ataxia may arise from acute deficiency of
tyrosine and dopamine

Decreased dendritic branching, hypomyelination



MSUD
Goals of Treatment

Restriction of Leucine, Isoleucine, and Valine to
maintain post-prandial plasma BCAA near
normal level
Supplement free valine and isoleucine
Give glutamine and alanine
Hemodialysis



MSUD
Goals of Treatment
Excessive restriction
Growth failure
Anemia
Breakdown of mucosa
Immunodeficiency
Dysmyelination, abnormal dendritic branching,
microcephaly and mental retardation



Follow-Up Jacob – Age 4 yr

Family unwilling to tolerate
Continual stress of life threatening disorder
dietary management, forcing feeds by G-tube when
not interested in eating)
Severe limitations on their lives



Liver Transplantation
Liver transplantation results in increase in
whole body BCKD activity
Muscle = 50%
Kidney = 25%
Liver and gut = 25%
Placed on liver transplant list at Pittsburgh
and underwent successful liver transplant 3
years ago
Now on unrestricted diet


Jacop after liver transplantation



Liver Transplant:
Outcomes

Normalization of
BCAA within 6-12
hours
Sustained
normalization of
BCAA on
unrestricted diet
(4-18 months f/u)
Strauss KA. Am J Transpl; 2006


Alkaptonuria
Alkaptonuria: a.k.a. Black Urine Disease
First recognized “Inborn Error of Metabolism”
by Archibald Garrod in 1902

Symptoms: Homogentisate in the urine oxidizes to a
black color
Also, black deposits in the sclera
In adults, accumulation of deposits
in connective tissue leads to arthritis

No effective treatment


Symptoms of alkaptonuria

Urine from patients
Normal urine with alkaptonuria


Patients may display painless bluish darkening of the outer ears,
nose and whites of the eyes. Longer term arthritis often occurs.



Homogentisic acid is an intermediate in the degradation pathway of
phenylalanine. The reaction is catalysed by homogentisate dioxygenase
(HGO).
homogentisic acid
OH

O O

HOOC C C
CH CH CH2 CH2 COOH
OH

HGO maleylacetoacetic acid
CH2

COOH

A deficiency of HGO causes
alkaptonuria.


Catabolic pathway for phenylalanine and
tyrosine

Defect here causes Homogentisate
dioxygenase
alkaptonuria

Defect here causes Fumarylacetoacetate
Type I Tyrosinemia hydrolase



Tyrosinemia
Tyrosinemia is diagnosed by a blood and urine test.
Tyrosinemia is treated by a low protein diet (low in
phenylalanine, methionine and tyrosine) and a drug
called NTCB.



homogentisic acid FAAH catalyses the last step in the
degradation path of phenylalanine and
tyrosine.

O O
Tyrosinemia
HOOC C C O O

=

=
CH CH CH2 CH2 COOH
HOOC - CH2 - CH2 - C - CH2 - C - CH2 - COOH

maleylacetoacetic acid
succinylacetoacetic acid
spontaneous
HOOC
CH CH CH2 CH2 COOH COOH
C C

O O O O

=

=
fumarylacetoacetate HOOC - CH2 - CH2 - C - CH2 - C - CH3

Succinylacetone
FAAH toxic and mutagenic

Fumarate + acetoacetate

Deficiency of the enzyme FAAH results in Type I tyrosinemia


WHAT ARE THE SYMPTOMS
OF
TYROSINEMIA?

The clinical features of the disease fall
into two categories:

Acute
Chronic



Acute tyrosinemia
• abnormalities appear in the
first month of life
• poor weight gain
• enlarged liver and spleen
• distended abdomen
• swelling of the legs
• increased tendency to
bleeding, particularly nose bleeds
• Jaundice
• death from hepatic failure
frequently occurs between three
and nine months of age unless a
liver transplantation is
performed.



Homocystinuria
Defective activity of cystathionine synthase



Major phenotypic expression

Ectopia lentis
Vascular occlusive disease
Malar flash
Osteoporosis
Accumulation of homocysteine and methionine



A family of homocystinuria



Albinism


What is Albinism?
A lack of pigment in skin, hair, and eyes.
Albinism is an inherited condition that
results from a gene mutation.
Altered genes are unable to exhibit natural
pigments that normally occur.
Albinism can occur in nearly all species:
animals, plants, or humans.



Albinism in all forms…



Lets take a closer look…
What causes Albinism?
Albinism is genetic and is
passed on through heredity via
the genes.
Genes involved are supposed to
communicate the pigmentation (Retina of albino)

of eyes, skin, and hair.
Albino Individuals have
received a recessive gene (aa)
from both parents resulting in
an incorrect genetic blueprint
for pigment.


Albinism



Characteristics of albinism:
Low Vision (20/50 to 20/800)
Sensitivity to bright light and
glare
Rhythmic, involuntary eye
movements
Absent or decreased pigment in
the skin and eye and sensitivity
to sunburn that could lead to
skin cancers or cataracts in
later life
"Slowness to see" in infancy



Characteristics of albinism:
Farsighted, nearsighted,
often with astigmatism
Underdevelopment of the
central retina
Decreased pigment in the
retina
Inability of the eyes to
work together
Light colored eyes ranging
from lavender to hazel,
with the majority being
blue



Problems associated with Albinism…

Impaired vision due to
the lack of melanin
pigment
Skin damage due to
Sun
Mild problems with
blood clotting
Hearing impairment



Classification & Types of Albinism

Oculocutaneous albinism (OCA): melanin
pigment is missing in skin, hair, and eyes.
Ocular albinism (OA): melanin pigment is
primarily missing in the eyes and the skin
and the hair appear normal.
OCA is more common than OA.



Oculocutaneous
Albinism



Genes Associated with Albinism
& Pigmentation:
Tyrosinase: major enzyme involved
in melanin formation
Location: Chromosome 11
DHICA-oxidase: loose of function
of this enzyme leads to albinism
Location: Chromosome 9
Ocular Albinism Gene: role
unknown
Location: Chromosome X (primarily
Sammy’s fault not Jeff’s)



Tyrosin hydroxylase

dopa

Tyrosin hydroxylase

dopaquinone

Eumelanins

Indole 5,6 quinone

Quinoleimine
intermediate
Mixed-type
melanins
Pheomelanins

trichochroms


Facts you may not know…
1 in 70 humans carries a Hey want to
know
recessive gene linked to something…
albinism.
If both parents carry an albino
gene the chances are 1 in 4 (½ x
½) that offspring will display
albinism. Not really,
but I
If one parent displays albinism, suppose
and one does not but carries a you are
recessive gene, the chances of going to
tell me
the offspring displaying anyway…
albinism is 1 in 2 (1 x ½). 132
June 26, 2012 Total slide. 122


Common Myths & Misconceptions

Persons with albinism always have red eyes.
Persons with albinism are totally blind.
Albinism is contagious.
Persons with albinism are the result of evil spirits
or wrongdoing.
Persons with albinism are retarded or deaf.
Albinism results from inbreeding or the mixture
of two races.
Persons with albinism have magical powers.



In summary…
Albinism is a rather
rare recessive
mutation that can be
witnessed in many
multiple species;
plant, animal, and
human, all with
phenotypic
similarities.



Albinism in animals



Albinism in films



A family of albinism



Newborn
screening



Newborn screening

The goal of newborn screening is to eliminate,
through early identification and treatment, and
improve the quality of life for affected
individuals.



Newborn screening

Newborn screening is not just a laboratory
service; it is a system of care including, not
only testing, but also follow up, definitive
diagnosis, treatment, long term management,
education and evaluation----



Newborn screening

The goal of newborn screening follow up is to
ensure that each affected infant receives the
full benefit of early detection and optimal
long term treatment and management.



Follow Up

short term follow up- assure that a definitive
diagnostic work-up is done, that the infant really
has the disorder and that the infant is started on
appropriate treatment
long term follow up- assure that the infant
continues to receive appropriate treatment and
monitors the long term outcome



THE END


Metabolic disorders of proteins

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