Genetics/Dysmorphology Flashcards
A 1 week old or newborn presented with poor feeding and vomiting then noted to be lethargic with hypertonicity and muscular rigidity with severe opisthotonos. What is the deficient enzyme? A. tyrosine B. galactose C. D. valine, isoleucine and leucine
D. NTP19 Ch 79 Defects in the Metabolism of Amino Acids
Classic MSUD
This form has the most severe clinical manifestations. Affected infants who are normal at birth develop poor feeding and vomiting in the 1st wk of life; lethargy and coma may ensue within a few days. Physical examination reveals hypertonicity and muscular rigidity with severe opisthotonos. Periods of hypertonicity may alternate with bouts of flaccidity. Neurologic findings are often mistaken for generalized sepsis and meningitis. Cerebral edema may be present; convulsions occur in most infants, and hypoglycemia is common. In contrast to most hypoglycemic states, correction of the blood glucose concentration does not improve the clinical condition. Routine laboratory findings are usually unremarkable, except for metabolic acidosis. Death usually occurs in untreated patients in the 1st few weeks or months of life.
Diagnosis is often suspected because of the peculiar odor of maple syrup found in urine, sweat, and cerumen (see Fig. 79-6). It is usually confirmed by amino acid analysis showing marked elevations in plasma levels of leucine, isoleucine, valine, and alloisoleucine (a stereoisomer of isoleucine not normally found in blood) and depression of alanine. Leucine levels are usually higher than those of the other 3 amino acids. Urine contains high levels of leucine, isoleucine, and valine and their respective ketoacids. These ketoacids may be detected qualitatively by adding a few drops of 2,4- dinitrophenylhydrazine reagent (0.1% in 0.1 N HCl) to the urine; a yellow precipitate of 2,4-dinitrophenylhydrazone is formed in a positive test. Neuroimaging during the acute state may show cerebral edema, which is most prominent in the cerebellum, dorsal brainstem, cerebral peduncle, and internal capsule. After recovery from the acute state and with advancing age, hypomyelination and cerebral atrophy may be seen in neuroimaging of the brain. The enzyme activity can be measured in leukocytes and cultured fibroblasts.
Treatment of the acute state is aimed at hydration and rapid removal of the branched-chain amino acids and their metabolites from the tissues and body fluids. Because renal clearance of these compounds is poor, hydration alone may not produce a rapid improvement. Peritoneal dialysis or hemodialysis is the most effective mode of therapy in critically ill infants and should be instituted promptly; significant decreases in plasma levels of leucine, isoleucine, and valine are usually seen within 24 hr of institution of treatment. Providing sufficient calories and nutrients intravenously or orally should reverse the patient’s catabolic state. Cerebral edema may need to be treated with mannitol, diuretics (e.g., furosemide), or hypertonic saline.
Treatment after recovery from the acute state requires a diet low in branched-chain amino acids. Synthetic formulas devoid of leucine, isoleucine, and valine are available commercially. Because these amino acids cannot be synthesized endogenously, small amounts of them should be added to the diet; the amount should be titrated carefully by performing frequent analyses of the plasma amino acids. A clinical condition resembling acrodermatitis enteropathica occurs in affected infants whose plasma isoleucine concentration becomes very low; addition of isoleucine to the diet causes a rapid and complete recovery. Patients with MSUD should remain on the diet for the rest of their lives. Liver transplantation has been performed in a number of patients with classic MSUD with promising results. These children have been able to tolerate a normal diet.
The long-term prognosis of affected children remains guarded. Severe ketoacidosis, cerebral edema, and death may occur during any stressful situation such as infection or surgery, especially in mid-childhood. Mental and neurologic deficits are common sequelae.
Most common congenital skeletal dysplasia: a. Achondroplasia b. Thanatophoric dysplasia c. (can’t remember) d. (can’t remember)
*NTP Chapter on D/o involving transmembrane receptors: The achondroplasia group represents a substantial percentage of patients with chondrodysplasias and contains thanatophoric dysplasia (TD), the most common lethal chondrodysplasia with an incidence of 1/35,000 births; achondroplasia, the most common nonlethal chondrodysplasia with an incidence of 1/15,000 to 1/40,000 births; and hypochondroplasia.
A patient with jaw swelling, irritability, fever, with anemia and elevated ESR:
a. Osteomyelitis
b. hypervitaminosis A
c. Rickets
d. Infantile cortical hyperostosis
d. Infantile cortical hyperostosis
* NTP18, Chapter 698: Also known as Caffey Disease. Manifestations include the sudden onset of irritability, swelling of contiguous soft tissue that precedes the cortical thickening of the underlying bones, fever, and anorexia. The swelling is painful with a woodlike induration but with minimal warmth or redness; suppuration is absent. There are unpredictable remissions and relapses; an episode may last 2 wk to 3 mo. The most common bones involved include the mandible (75%) ( Fig. 698-4 ), the clavicle, and the ulnar.Laboratory features include elevated erythrocyte sedimentation rate and serum alkaline phosphatase as well as in some patients increased serum prostaglandin E levels. There may be thrombocytosis and anemia.
When is the best time to repair a cleft lip, as long as the infant has shown satisfactory weight gain?
a. 12 months
b. 1 month
c. 3 months
d. 5 years
C. 3 mos
NTP: Surgical closure of a cleft lip is usually performed by 3 mo of age, when the infant has shown satisfactory weight gain and is free of any oral, respiratory, or systemic infection. Modification of the Millard rotation-advancement technique is the most commonly used technique; a staggered suture line minimizes notching of the lip from retraction of scar tissue. The initial repair may be revised at 4 or 5 yr of age. In an otherwise healthy child, closure of the palate is usually done before 1 yr of age to enhance normal speech development.
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