Aminoacidopathies Flashcards
4 parts of amino acid structure
Amino group
Carboxylic group
Side chain
Hydrogen atom
3 “pathways” for amino acids
Anabolism
Conversation
Excretion
Enzyme deficient in PKU
Phenylalanine hydroxylase
Gene and inheritance in PKU
PAH, AR
Treatment for PKU
Dietary phe restriction
Dietary phe-free protein formula
Sapropterin
Oral form of BH4
Less response in those with no enzyme activity
Phenylalanine Ammonium Lyase Injection
Enzyme catalyzes alternative phe degradatio pathway
Large neutral aa
Compete with phe at the BBB to block phe entry into the brain
Risks with maternal PKU
Microcephaly, MR
IUGR
CHD
Tyrosinemia Type 1 enzyme deficiency
Fumarylacetoacetate hydrolase
Tyrosinemia Type 1 inheritance and gene
AR, FAH
Tyrosinemia treatment
Dietary phe and tyr restriction
Dietary supplement with phe/tyr-free formula
nitisinone
Liver transplant
MSUD enzyme deficiency
Branch chain keto-acid dehydrogenase deficiency
MSUD inheritance and gene
AR, BCKDHA/BCKDHB/DBT/DLDE3
MSUD Treatment
BCAA- free calories
Thiamine supplementation
Hemodialysis/hemofiltration
Homocystinuria enzyme deficiency
Cystathionine beta-synthase
Homocystinuria inheritance and gene
AR, CBS
Treatment of Homocystinuria
Restrict met
Met-free formi.a
Supplements to use to homocystinuria
Vit b6
Betaine
Non-ketotic hyperglycemia enzyme deficiency
Glycine cleavage enzyme
NKH inheritance and gene
AR, GLDC/AMT/GCSH
Treatment for NKH
Sodium benzoate
Dextromthorphan
Glycine restriction
Untreated PKU in Neonatal Period
Fair skin and hair pigmentation
Mousy/Musty odor
Untreated PKU after infancy
Developmental delay
Autism, microcephaly, behaviour issues
Many with epilepsy, eczema
PKU plasma AA
Increased Phe
Increased phe to tyr ratio
PKU prenatal testing
Possible if familial mutation known
Untreated Tyrosinemia Type 1 in infancy
Cabbage-like odor to urine
Liver and renal dysfunction
Rickets, poor growth
Neurologic crises
Untreated Tyrosinemia Type 1 after infancy
Typically death by age 10
Tyrosinemia Type 1 plasma AA
Elevated tyr
Elevated succinylacetone in blood
Prenatal dx of Tyrosinemia Type 1
Molecular testing if familial mutation known
Succinylacetone measured in amniotic fluid
Untreated MSUD 12-24 hours after birth
Maple syrup odor in urine and ear wax
Untreated MSUD 5 days after birth
Irritability and decreased feeding
Encephalopathy/ cerebral edema
Untreated MSUD 7-10 days after birth
Coma
Respiratory failure
Death in weeks
MSUD AA profile
Elevated: leucine, isoleucine, valine
Presence: allo-isoleucine
MSUD prenatal dx
Molecular testing if familial mutation is known
BCKD enzyme activity on amnio/CVS
Untreated Homocystinuria Features
Marfanoid skeletal changes
Ectopia lentis
Neuropsychiatric disease
Veinous/Arterial Thromboembolism
Homocystinuria plasma AA
Elevated: homocysteine and methionine
Low/absent: cysteine
Untreated NKH symptoms
Intractable neonatal seizures
Hypotonia
Encephalopathy within first few days of life
NKH plasma AA
Abnormal CSF to plasma glycine ratio
Prenatal Dx for NKH
Molecular testing of familial mutation
Prenatal dx for Homocystinuria
Molecular testing of familial mutation
CBS enzyme activity assay in amniocytes (not CVS)
Amniotic fluid homocysteine levels
