Ped Metabolic Illness Flashcards
How common are pediatric metabolic disorders?
1/200
What is the prognosis for most of the pediatric metabolic disorders?
Lethal
What common condition mimics pediatric metabolic disorders?
Sepsis
Birth trauma
HF
What are the three conditions in which a metabolic disorder must be suspected?
- Neonates with unexplained, progressive disease after normal pregnancy
- All children with acute deterioration of general condition
- Children with ssx of acidosis or hypoglycemia
What is the inheritance pattern of Type II hyperlipoproteinemia?
AD
What is the inheritance pattern of Polycystic kidney disease?
AD
What is the inheritance pattern of G6PD deficiency?
XLR
What is the inheritance pattern of Hunter syndrome? What enzyme is defective in this? What metabolites accumulate? SSX?
XLR
iduronate-2-sulfatase (I2S).[1][2] The accumulated substrates in Hunter syndrome are heparan sulfate and dermatan sulfate
GAG buildup in face and abdo, but no eye
What is the inheritance pattern of Duchenne’s muscular dystrophy? What is the pathophysiology of this?
XLR
Mutation in the dystrophin gene that is a part of the skeletal framework of muscle cells
What is the inheritance pattern of Hurler’s syndrome? What enzyme is defective in this? What metabolites accumulate? SSX?
XLR
alpha-L iduronidase
Heparan sulfate and dermatan sulfate
MR, eye issues
What is the most important part of the history to obtain if you suspect an inherited disorder of metabolism
Diet history
What are the ssx of inborn?
Hypoglycemia
Metabolic acidosis
Lactic acidosis
Hyperammonemia
Diaphoretic newborns should be suspicious for what?
IEM
What is the ULN of ammonia for infants? How does this compare to adults?
95 Much higher than adults (35)
What are the ssx of hyperammonemia?
Lethargy
Somnolence
Emesis
Szs
What, generally, is the usual cause of hyperammonemia in children?
Urea cycle issues
What is the drug of choice for treating seizures in infants? MOA?
Phenobarbital
increased flux of chloride ions into the neuron d/t increase in Cl channel opening duration
What is MCAD deficiency? Cause? Ssx?
- AR, Medium-chain acyl-CoA dehydrogenase deficiency
- hypoketotic hypoglycemia and liver dysfunction, often preceded by extended periods of fasting or an infection with vomiting.
What is the most common cause of sepsis in newborn females?
UTI
What is the cause of PKU? SSX?
Deficiency in phenylalanine hydroxylase, causing a musty baby odor, and MR if not treated
What is the amino acid that pts with PKU must avoid? What must they take a supplement for?
Avoid F
Increase Y
What is the inheritance pattern of PKU?
AR
How do you diagnose PKU?
Plasma Phe level more than 20 mg/dL
What is the treatment for PKU?
Restrict F intake
Lofenalac
What is Lofenalac?
Baby formula that lacks phenylalanine for PKU pts
What is malignant hyperphenylalaninemia?
normal phenylalanine hydroxylase (PAH) activity but have a deficiency in dihydropteridine reductase (DHPR), an enzyme required for the regeneration of tetrahydrobiopterin (THB), a cofactor of PAH
What are the early ssx of PKU?
- Choking spells with trying to swallow
- Vomiting
- Abnormal neurological development
What are the Phe levels for mild, moderate, and severe PKU?
Mild = less than 600 Mod = 600-1200 Severe = 1200+
What is the inheritance pattern of PKU?
AR
What is the incidence of PKU?
1:15000
What is the allowable amount of Phe for PKU pts?
250-350 mg
What are the ssx of maternal PKU (untreated PKU in the mother)?
Microcephaly
Low birth weight
MR
What level of Phe in a PKU mother is bad for the infant?
More than 360 microM
What is the cause of galactosemia? Inheritance? Ssx?
- AR
- Galactokinase, or galactose-1-uridyl transferase
- ssx: hepatomegaly, MR, cataracts,
What causes the cataracts in pts with galactosemia?
High galactose levels are converted in eye by aldose reductase to galactitol, but this is not suitable for polyol dehydrogenase (the next enzyme in the pathway) so builds up.
What is the incidence of galactosemia?
1:75000
What is the usual presentation of children with galactosemia?
Physically normal at birth, but vomiting, diarrhea, HSN, jaundice and cataracts
What type of bacteria are patients with galactosemia susceptible to?
Gram negatives
What is the urinary finding of galactosemia?
Reducing substance (sugar)
What is the test to confirm galactosemia?
Red cell enzyme test
What is the treatment for galactosemia?
Avoid breast milk and other sources of galactose—soy formula
What is the prognosis for galactosemia?
Mortality in neonatal period of 20%, but good if treated
What are the three major things to monitor for with pts with galactosemia?
- E. coli sepsis risk
- Treat jaundice PRN
- Monitor for developmental delay
What is the presentation of MCAD deficiency?
Emesis after periods of fasting (sleeping)
What are the pH, pCO2, and HCO3 levels with organic acidemias? Urea cycle disorders?
All low for organic acidemias
pH is high with urea cycle disorders, but HCO3 and pCO2 are low
What is the cause of homocystinuria? What is the enzyme that causes this involved in? Ssx?
Deficiency in cystathionine beta synthase–involved in the pathway of converting methionine to cysteine
Dislocation of optic lens, MR,
What is the treatment for homocystinuria?
B6 supplementation
What is the cofactor needed for Phenylalanine hydroxylase?
DHP
How does PKU cause MR?
Inhibits the transport of other amino acids across the BBB
What molecule can all glucogenic amino acids be broken down into? Ketogenic?
- Oxaloacetate = glucogenic
- Acetyl-coa
What are the two purely ketogenic amino acids?
Leucine
Lysine
What is familial hyperinsulinemic hypoglycemia type 6?
Insensitivity of E-dehydrogenase, leading to continued catabolism of AAs. The increase in ATP leads the pancreas to overproduce insulin, causing hypoglycemic hyperinsulinemia
What is the only reaction in the body N5-THF back to THF? What enzyme catalyzes this reaction?
Conversion of homocysteine to methionine
Methionine synthase
What is the cause of maple syrup urine disease?
Inability to break down branched chain amino acids (Isoleucine, Leucine, Valine)
(“I Love Vermont Maple syrup”)
What is alkaptonuria, and what causes it? SSx?
- Homogentisate oxidase defect
- Urine turns black on exposure to air, and ochronosis
What is the molecule that can be donated from the urea cycle to the TCA cycle?
Fumarate
What is the molecule that can be donated from the TCA cycle, to the urea cycle?
OXA –(AST)– D
(AST) is the enzyme
What is the cause of citrullinemia? Ssx? Treatment?
Defect in argininosuccinate synthetase,
What is the cause of argininosuccinic aciduria? Ssx? Treatment?
Defect in argininosuccinate lyase
What is the cause of hyperargininemia? Ssx? Treatment?
Arginase deficiency
What is the major difference between hyperargininemia and other urea cycle defects?
Build up of ammonia leads to hepatic encephalopathy
What is Adrenoleukodystrophy? What is the classical presentation? Prognosis? Gene?
ABCD1 gene–XLR disorder of peroxisomal beta-FA degradation. Leads to neuropathy d/t FA accumulation.
Young male with acidosis, Hyperkalemia, hypotension, and neurological ssx.
