Amino Acidopathies, Urea Cycle Defects & Organic Acidemias

PKU, Tyrosinemia, Maple Syrup Urine disease, Homocystinuria, and Glycine encephalopathy are examples of (amino acidopathies, urea cycle defects or organic acidemias)

Amino acidopathies

NAGS deficiency, CPS1 deficiency, OTC deficiency, Citrullinemia type 1, ASA lyase deficiency, and arginase deficiency are examples of (amino acidopathies, urea cycle defects or organic acidemias)

Urea cycle defects

Propionic acidemia, biotinidase deficiency, holocarboxylase deficiency, methylmalonic acidemia, cobalaminopathies, glutaric aciduria, and isovaleric acidemia are examples of (amino acidopathies, urea cycle defects or organic acidemias)

organic acidemias

Labs for PKU would show high ___ and low ___

High Phe and low Tyr

hyperPhe would result in (classic or nonclassic) PKU

classic

Untreated PKU would result in which symptoms

• vomiting

• irritability

• eczematous rash

• musty odor

• abnormal EEGs

• fairer complexion than relatives

• irreversible ID

Treated PKU would result in which symptoms

• rates of ID and suboptimal cognitive outcomes

• psychiatric diagnoses correlated with metabolic control

Uncontrolled maternal PKU would result in what symptoms for the fetus

• fetal growth restriction

• microcephaly

• CHD

• ID

• can be confused for fetal alcohol syndrome

Treatment for PKU

• limitation of Phe intake with metabolic formula

• protein restriction

• provide tyrosine

Tyrosinemia type 1 is due to a deficiency in which enzyme?

• fumarylacetoacetate hydrolase (FAH)

Tyrosinemia type 1 symptoms

• renal fanconi —> rickets

• porphyric pain crises

• hepatomegaly, liver failure, hepatocellular carcinoma

Treatments for tyrosinemia type 1

• Tyr-restricted diet

• protein restriction

• NTBC

• liver transplantation

Pathology of tyrosinemia type 1 is due to an accumulation of toxic ___ and ___

• succinylacetone

• fumarylacetoacetate

Maple syrup urine disease is due to a deficiency in branch chain ___

• ketoacid dehyrogenase

Symptoms of maple syrup urine disease

• leucine encephalopathy

• poor feeding

• lethargy

• irregular breathing

• loss of primitive reflexes

• dystonia

• seizures

Labs of maple syrup urine disease would show:

• ketoacidosis

• elevated branch chain amino acids

Treatment of maple syrup urine disease would include:

• dietary restriction of branch chain amino acids

Homocystinuria is due to a deficiency in the enzyme ___

• cystathionine B-synthase (CBS)

Homocystinuria symptoms

• ectopia lentis

• severe myopia

• thromboembolism

• marfanoid habitus but w/o hypermobility

• ID

Homocystinuria labs on newborn screen would show elevated ___ and ___

• homocysteine

• methionine

Glycine encephalopathy genes (2)

• GLDC

• AMT

• deficiency in glycine cleavage system —> excessive stimulation of excitatory glycine receptor on the NDMA glutamate receptor channel complex —> neurotoxicity

Glycine encephalopathy symptoms

• intractable neonatal seizures

• apneic episodes

• absent/minimal developmental progress

• history of in utero hiccups

Endogenous recycling: proteins are constantly degraded back to ____ and used to reconstitute ___

• amino acids

• proteins

Where does the urea cycle occur?

• liver

The urea cycle is a major metabolic pathway that detoxifies waste ___ formed during protein metabolism

• nitrogen

The urea cycle is a 5 step pathway which results in conversion of 2 molecules of ___ and 1 of bicarbonate to urea

• ammonia

Neonatal onset symptoms of urea cycle defects

• w/in 24 hours of life

• irritability

• poor feeding, vomiting

• lethargy

• hypotonia

• seizures

• respiratory distress, apnea

• liver dysfunction

• coma, death

Later onset symptoms of urea cycle defects

• neuropsychiatric symptoms: hyperactivity, self-injurious behavior, hallucinations

• protein avoidance

• developmental delay

• seizures, stroke, ataxia, vision loss

• episodic hyperammonemia

• when severe: lethargy, delirium, coma, death