PEM Flashcards
What are the two types of PKU?
PAH deficient (97%) Non PAH deficient (3%) -defects in tetrahydrobiopterin (BH4) or other components in related pathways -BH4 is a cofactor for many hydroxylases
What are the characteristics of PKU
elevated levels of Phe in tissues, plasma and urine
- Elevated levels of phenylketones
- CNS symptoms - mental retardation, failure to walk or talk, seizures, hyperactivity, tremor, microcephaly, failure to grow
- IQ below 50
- Hypopigmentation
What are the phenylketones?
phenylpyruvate
phenylacetate
phenyllactate
What is causing neurotoxicity?
Decreased brain protein synthesis
Phenylketones not ccrossing into brain
Phe and metabolites compete for transport across the blood brain barrier
Decreased production of catecholamines
WHat is important in the synthesis of catecholamines?
Tyrosine
Diagnostic criteria of PKU?
Normal blood phe levels (120-360 umol/L)
PAH deficient: Mild (600-1200) Classical (>1200)
Non PAH deficient - <600 umol/l
Guthrie Bacterial inhibition assay
Confirmation of diagnosis
Treatment for PKU?
Reduce phenylalanine intake
Tyrosine supplementation
Maternal PKU - keep level < 10 mg.dl
PKU Initial medical nutrition therapy
7-10 days old phenalanine free formula -Infants and toddlers --90% protein requirements --80% energy requirements Reliable source of vitamins and minerals Supplement evaporated milk, regular infant formula, or breast milk during infancy and early childhood
Later medical nutrition therapy for PKU
Low phe content foods introduced at the appropriate age and used as a supplement to the formula mixture
-5-6 months: pureed food
7-8 months: finger foods
PKU clinical management
- Monitoring - clinical (growth and cognitive development) and biochemical (plasma Phe 2-6 mg) & tyrosine
- Education about management
- Counseling - importance of continuing therapy
PKU management challenges
- Early recognition and initiation of therapy
- Achieving nutritional balance and minimizing iatrogenic nutritional deficiencies (minimal Phe requirement)
- Adherence to treatment regimen
- Adolescence and adulthood
What is maple syrup urine disease?
Defective metabolism of three amino acids (leucine, valine and isoleucine) as a result of defective a-ketoacid dehydrogenase
clinical signs present by 4 or 5 days
Symptoms of maple syrup urine disease
Urine has odor of maple syrup poor suckling, irregular respiration, periodic flaccidity acidosis neurological deterioration depressed growth seizures lower life span
MSUD clinical management
- Medication/supplementation - formulas and medical foods low in branched chain amino acids, supplement valine and isoleucine
- Dietary modification - low BCAA foods
- monitoring - clinical ( growth and development) and biochemical (plasma BCAA concentrations)
- Education about management (sick day management)
- COunseling - continuance of therapy
MSUD management challenges ?
- Early recognition and initiation of therapy
- Achieving nutritional balance and minimizing iatrogenic nutritional deficiencies (minimal isoleucine and valine requirement)
- Adherence to treatment regimen
- Adolescence and adulthood
What is Galactosemia?
Inherited disorder
Affects the way the blood breaks down lactose due to lack of enzyme galactose-1-phosphate uridyl transferase (GALT)
GAlactose buildup becomes toxic
LActose is broken down in the body into galactose and glucose
Serious health problems caused by galactosemia
swollen and inflamed liver, kidney failure, stunted physical growth and mental growth, and cataracts in the eye
70% chance of death if it is not treated
Hepatic and GI manifestation of Galactosemia
Lethargy, irritability and hypotonia
feeding difficulty and poor weight gain
jaundice, hypoglycemic, hepatomegaly
hepatic damage
Other manifestations of Galactosemia
Polydypsia, polyurea rickets Mental retardation Seizure Coagulation abnormalities Fulminant e-coli spesis
Clinical management of Galactosemia
- Medication/supplementation - lactose free formulas; treatment of acute illness (sepsis)
- Dietary modifications - Restriction of all milk and milk products and lactose containing foods
- Restriction of some fruits and vegetables are controversial - monitoring - clinical (growth and cognitive development)
- Education about therapy and management
- Counseling
Testing for Galactosemia
Positive clinitest and negative clinitest
Urine galactose by chromatography
Direct hyperbilirubinemia
RBC’s galactose 1 phosphate uridyl transferase activity
Increased galactose 1 phosphate in RBC
What are the 6 newborn screening for IEMs
congenital adrenal hyperplasia (CAH) congenital hypothyroidism (CH) Galactosemia (GAL) Maple syrup urine disease (MSUD) Phenylketonuria (PKU) Sickle cell disease and other hemoglobinopathies (HGB)
What is the cofactor for maple syrup urine disease?
Thiamine
What is the cofactor for PKU?
bH4
