Pediatrics Flashcards
Baby presents with jaundice, voiting, irritability, and somnolene after switching from breastmilk to baby food. Labs show hypoglycemia, ketosis, and reducing sugars in urine. What is the most likely diagnosis.
Based on timecourse (switch from breastmilk), hypoglycemia and urine sugars, suspect aldolase B deficiency (aka hereditary fructose intolerance)
In this disorder, fructose-1-P accumulates. It depletes the cell’s ATP stores and causes phosphate trapping. Without ATP, gluconeogenesis and glycogenolysis stop working, leading to hypoglycemia, vomiting, and liver problems such as hepatomegaly, jaundice, and even cirrhosis.
What are the key enzymes in fructose metabolism?
Fructose first enters liver cells through the GLUT-5 transporter, which works via facilitated diffusion. Then the following enzymes work their magic, in order:
Fructokinase: Conversion of fructose to fructose-1-P. This step requires adenosine triphosphate (ATP) to provide the phosphate.
Aldolase B: Cleavage of fructose-1-P to dihydroxyacetone phosphate and glyceraldehyde.
Triose phosphate isomerase and triose kinase: Conversion of dihydroxyacetone phosphate and glyceraldehyde to glyceraldehyde-3-P.
Glyceraldehyde-3-P can then proceed through glycolysis as usual
What problems occur downstream of aldolase B deficiency
aldolase converts fructose-1-P to metabolites, therefore its deficiency leads to fructose-1-P accumulation. It depletes the cell’s ATP stores and causes phosphate trapping. Without ATP, gluconeogenesis and glycogenolysis stop working, leading to hypoglycemia, vomiting, and liver problems such as hepatomegaly, jaundice, and even cirrhosis. Fructose-1-P also competitively inhibits glycogen phosphorylase, the first step in glycogenolysis, thus exacerbating hypoglycemia.
What types of sugars should be avoided in patients with fructose metabolism disorders?
fructose, sucrose, sorbitol
describe galactose metabolism
Galactose enters cells through SGLT1, the same sodium-dependent transporter used to take up glucose. Inside cells, galactose metabolism proceeds with the help of the following enzymes (Figure 2):
Galactokinase: Converts galactose to galactose-1-P. This step requires ATP to provide the phosphate.
Galactose-1-phosphate uridylyltransferase (GALT): Converts galactose-1-P to glucose-1-P by switching the attached groups of galactose-1-P and UDP-glucose. In Figure 2, this enzyme is labeled simply as uridylyltransferase.
Aldose reductase: Converts galactose to galactitol via the polyol pathway. This is the same enzyme that converts glucose to sorbitol.
what enzyme is deficient in maple syrup urine disease
Alpha-ketoacid dehydrogenase (ie branched chain alphe ketoacid dehydrogenase or BCKDH)
Normal serum Ammonia in the setting of a suspected inborn error of metabolism would rule out which ones?
excludes a urea cycle disorder or an organic acidemia.
presence of ketones in the urine in the setting of a suspected inborn error of metabolism would rule out which ones?
rules out a beta-oxidation disorder which would cause hypoketosis
what are the key features and types of urea cycle disorder
Key features include
- presentation in the first 24-48 hours after birth (b/c breastmilk contains proteins)
- severe hyperammonemia,
- absence of acidosis or other metabolic derangements.
The most common urea cycle disorder is the deficiency of the enzyme ornithine transcarbamylase –> As a result, ammonia cannot be metabolized into urea
Many inborn errors of metabolism present in the first few days of life. Two key exceptions are (1) ______________ and (2) ________________
Two key exceptions are (1) glycogen storage disease type I (usually 3 to 6 months) and (2) hereditary fructose intolerance (occurs when weaned from breastfeeding).
what infection is characterized by the Triad of: hydrocephalus, intracranial calcifications, and chorioretinal lesion
toxoplasmosis
what TORCH infection is characterized by triad of: hearing loss, patent ductus arteriosus (continuous murmur), and cataracts
rubella
mn: a murmur sounds like a RUBbing noise (RUBella)
+ssRNA virus
what TORCH infection is characterized best by: sensorineural hearing loss, hepatosplenomegaly +/- jaundice, thrombocytopenia, microcephaly
CMV
By what age(s) do the primitive reflexes typically disappear?
Moro reflex by 3 months, rooting reflex by 4 months, palmar reflex by 6 months, and Babinski sign by 12 months of age (the Babinski reflex disappears when the corticospinal tract becomes myelinated)
**note these ages are all factors of 12
what are the two key causes of failure to pass meconium within first 48 hrs of life
cystic fibrosis and Hirschsprung disease
What is the biochemical profile for OTC deficiency?
OTC deficiency = ornithine transcarbamylase deficiency
OTC converts Ornithine and carbamoyl phosphate to citrulline
Profile: hyperammonemia, ketosis, urine orotic acid, absent hypoglycemia, absent acidosis
What is the biochemical profile for PDC deficiency?
PDC = pyruvate dehydrogenase complex
converts pyruvate to acetyl CoA
Profile: alanine in urine and serum, hyperammonemia, severe lactic acidosis, high serum pyruvate
What is the biochemical profile for Lesch Nyhan syndrome?
This syndrome is a deficiency in hypoxanthine-guanine phosphoribosyl transferase (HGPRT), which catalyzes the conversion of Hypoxanthine and phosphoribosyl pyrophosphate to inosine monophosphate
Profile: uric aciduria, absent hyperammonemia.
sx: renal calculi, neurologic dysfunction (spasticity), delayed physical and mental development, self-injurious behavior (bruising), hemolytic anemia, and immune deficiency manifesting after 6 months of life.
What is the biochemical profile of phenylketonuria (PKU)
deficiency of Phenylalanine hydroxylase
converts phenylalanin –> tyrosine
intellectual abnormalities, seizures (from decreased tyrosine), growth retardation, dermatitis, fair skin, or a musty body odor
Profile: elevated serum phenylalanine (+phenylacetate in urine), absent hyperuricemia, absent hyperammonemia
Tyrosine is nutritionally essential to patients with PKU and must be supplemented.
Orotic acid concentrations are increased in patients with ________________ and _____________________
uridine monophosphate synthase deficiency (orotic aciduria) or ornithine transcarbamylase (OTC) deficiency.
which enzyme deficiency (IEM) can cause severe combined immunodeficiency
adenosine deaminase deficiency
what is the biochemical profile for MCAD deficiency?
Medium-chain acyl-CoA dehydrogenase (MCAD) degrades medium-chain fatty acids into acetyl-CoA in the mitochondria (β-Oxidation)
in patients with MCAD deficiency, a deficit of acetyl-CoA develops, which leads to hyperammonemia, hypoglycemia without compmensatory ketosis, vomiting, and lethargy, (usually presenting after period of fasting or high ATP demand such as infection)
What is the biochemical profile for OTC deficiency
Ornithine transcarbamylase deficiency (OTC)
Converts ornithine and carbamoyl phosphate to citrulline
Buildup of carbamoyl phosphate → orotic acid
Profile: orotic acid in the urine, hyperammonemia, failure to thrive, developmental delay
don’t confuse with orotic aciduria which does not present with hyperammonemia
which IEM are autosomal recessive
basically all the urea cycle disorders
