CMB Exam 2 - Diseases Flashcards
Tyrosinemias Type II and III
More benign than type I, because blockage happens earlier in the pathway and succinylacetone is not produced. May result in keratitis (severe visual disturbances) and hyperkeratosis of palms and soles. Treatment with a restricted phenylalanine/tyrosine diet is effective.
classic galactosemia
Due to loss of uridylyltransferase (GALT). Typically presents in the first weeks after birth; presents with poor feeding, weight loss, vomiting, diarrhea, lethragy; hepatomagaly, jaundice, and bleeding disorders; renal tubule disease; can lead to blindness. SSx resolve upon galactose restriction.
Cystinuria: treatment
Penicillamine and other compounds increase the solubility of cystine by complexing with it.
Tyrosinemia Type I: screening and diagnosis
After an abnormal neonatal screen, check quantitative plasma tyrosine and blood/urine succinylacetone. Diagnosis is confirmed by increased concentration of succinylacetone. Some DNA testing is available as well.
ASL deficiency: diagnosis
Elevated citrulline in screen, elevated argininosuccinate in the urine.
type VI glycogenosis
(Hers disease; liver phosphorylase deficiency) Hepatic-hypoglycemic glycogen storage disease, ketonuria. Probably good prognosis.
Mutations in which genes cause neonatal diabetes mellitus?
KCNJ11 and ABCC8 (subunits of the ATP-sensitive potassium channel) and others.
type IV glycogenosis
(Andersen disease; branching enzyme deficiency) Presents with hepatic cirrhosis and early liver failure, but doesn’t directly affect blood glucose levels. Prognosis is usually death within the first year.
hyperkeratosis
Abnormal thickening of the skin. Can result from tyrosinemia types II and III.
plasma acylcarnitine profile
Excessive intermediates of fatty acid oxidation and organic acid catabolism are conjugated with carnitine, so the plasma acylcarnitine profile reflects this accumulation.
essential fructosuria
Benign condition resulting from a deficiency of fructokinase. Characterized by hyperfructosemia and fructosuria.
Andersen disease
Type IV glycogenosis; branching enzyme deficiency. Presents with hepatic cirrhosis and early liver failure, but doesn’t directly affect blood glucose levels. Prognosis is usually death within the first year.
Tyrosinemia Type I: SSx
Accumulated liver metabolites, bleeding disorder, hypoglycemia, hypoalbuminemia, elevated transaminases, and defects in renal tubular function. May cause hepatocellular carcinoma.
What effect can cystic fibrosis have on protein metabolism? What is the treatment?
Defective chloride channels cause inspissations of pancreatic exocrine secretion, obstructing enzyme release. Treatment is supplementation of pancreatic enzymes with each meal.
galactosemia
Due to loss of galactokinase (GALK). Can result in cataracts and/or blindness. SSx resolve upon galactose restriction.
OTC deficiency: inheritance
X-linked.
Which of the glycogenoses is predominantly hepatic-hypoglycemic?
Types I (Ia - von Gierke disease - and Ib), VI (Hers disease), and VIII. Type III (Forbes disease) does muscle AND liver. These patients tend to present with hepatomagaly and hypoglycemia.
OTC deficiency: SSx
High neonatal mortality in males. In females, SSx can include hyperammonemia, recurrent emesis, lethargy, seizures, developmental delay, and episodic confusion. They may spontaneously limit protein intake.
type II glycogenosis
(Pompe disease; lysosomal α-glucosidase deficiency) Myopathic. Presents with cardiomegaly, symmetrical muscle weakness, heart failure, and a shortened P-R interval. Prognosis is usually death in first year; enzyme therapy is available but expensive.
metabolic alkalosis
Increase in blood HCO3- (eg vomit out your acid, exogenous bicarb/antacids, respiratory compensation (hypoventilation increases both H+ and HCO3-). Resulant hypokalemia can depolarize neurons.
MSUD: enzyme deficiency
(branched chain ketoaciduria) A deficiency of the decarboxylase initiates the degradation of the ketoacid analogs of the three branched chain amino acids—leucine, isoleucine, and valine.
What qualify as elevated glucose levels?
> 126 mg/dL fasting, >200mg/dL post-prandial (especially on 2 occasions, 2 hours after 75g dose of glucose (OGTT)
metabolic acidosis
Usually caused by influx of (exogenous) organic acid. HCO3- tends to drop.
epimerase deficiency
(GALE) 1 of 3 kinds of galactose intolerance. Has 2 forms: the benign one is in erythrocytes, the severe looks like GALT deficiency (ie GI issues, liver issues, kidney issues, potential blindness).