Question

A newborn girl appeared normal at birth, but within 24 hours she developed lethargy, hypothermia, and apnea. The attending physician suspects a metabolic disorder and orders a panel of labs. Which diagnostic would be the best to distinguish between a urea cycle disorder and a disorder in β -oxidation? (Please discuss your rationale for this choice) a. Blood glucose b. Urinary acids c. Serum fatty acids d. Plasma glutamine

A full blood work up was ordered for this female and the data is presented below. ● The initial blood ammonia level was elevated at 314 ug/dl (normal range = 17–80) and rapidly rose to 600 ug/dl. ● The urine orotic acid level was markedly elevated at 473 umol/L creatinine (nl = 0–3). ● The plasma citrulline level was normal at 10 uM/L (nl = 12–55). In this patient where orotic acid levels are elevated, list one urea cycle enzyme that is most likely deficient and one urea cycle enzyme that is least likely to be impaired. (Be sure to justify your answers)

Answer 1

Urea Cycle Disorder (UCD) A urea cycle disorder (UCD) is an inherited disease that affects how the body removes the waste that is made from breaking down protein. ... In a healthy person, the liver supplies several enzymes to change nitrogen into urea, which is then removed from the body in urine.

Beta-Oxidation Cycle Disorders. In these processes, there are numerous inherited defects, which typically manifest during fasting with hypoglycemia and metabolic acidosis; some cause cardiomyopathy and muscle weakness. ... Acetyl CoA is generated from fatty acids through repeated beta-oxidation cycles.

Symptoms of Newborns with Urea Cycle Defects

Normal appearance at birth

Irritability progressing to somnolence, lethargy, then coma

Loss of thermoregulation (hypothermia)

Feeding disruption (increases catabolism)

Neurologic posturing (from cerebral edema

Seizures

Hyperventilation and then hypoventilation

The most important step in diagnosing urea cycle disorders is clinical suspicion of hyperammonemia. A blood ammonia level is the first laboratory test in evaluating a patient with a suspected urea cycle defect

The following FAODs are diagnosed by newborn screening: CACT deficiency, CPT II deficiency (neonatal and late onset), VLCAD deficiency, MCAD deficiency, SCAD deficiency and a few other disorders like electron transport flavoprotein-ubiquinone oxidoreductase (ETF-QO) deficiency, α-ETF deficiency and β-ETF deficiency