The following CASE REPORT is given:
This 3 1/2-year-old boy was born to nonconsanguineous parents from Chihuahua, Mexico after an uncomplicated pregnancy and delivery. A brother had died at 3 months of age of a "liver problem" after an unexplained coma. The parents and three siblings are well.
At 3 months of age the boy was admitted in coma to a community hospital and suffered a cardiac arrest. Examination revealed hepatomegaly and cardiomegaly and a serum glucose of 15 mg/del (normal, 60-100 mg/dl). The patient eventually recovered and the hepatomegaly resolved. At 6 months of age he developed congestive heart failure after an upper respiratory tract infection and was brought o the medical center of the University of California, Los Angeles. Hepatomegaly and hypotonia were noted on admission. ON day 3 he became lethargic and developed generalized seizure activity and cardiac arrest, but he was successfully resuscitated. Laboratory studies at the time of the arrest revealed a blood glucose level of 15 mg/dl without associated acidosis or ketosis; mild elevation of serum aspartate aminotransferase (SGOT) (337 I.U./liter; normal, 6-36 I.U./liter) and alanine aminotransferase (SGPT) (179 I.U./liter; normal, 10-45 I.U./liter); and hyperammonemia (300 ug/dl; normal <69 ug/dl). Delayed milestones (developmental quotient 66; normal, 100), proximal-muscle weakness, and growth retardation (weight and height below the 3rd percentile) were noted after recovery. Metabolic studies showed normal glucose, galactose, and fructose tolerance, and a normal 10-hour fasting blood glucose, with no increase in lactate, pyruvate, or ketone bodies. The electroencephalogram, brain scan, and chromosomal studies were unremarkable. Also normal were the plasma levels of electrolytes, calcium, phosphorus, magnesium, bilirubin, thyroxine, thyroid-stimulating hormone, and growth hormone. Results of total serum protein determination, serum electrophoresis, cerebrospinal fluid studies, and studies of immune function were also normal. Between acute episodes, serum levels of glucose, ammonia, SGOT, SGPT, and creatine phosphokinase were all normal.
The patient was again admitted with cardiorespiratory arrest after upper respiratory tract infections at the ages of 20, 24, and 33 months. The episodes were associated with liver enlargement, elevations of transaminases to >2000 I.U./liter, and of creatine phosphokinase from 1500 to 33,000 I.U./liter. Maintenance glucose requirements varied from normal (3 mg/kg of body weight per minute) to slightly elevated (5-7 mg/kg/min).
A muscle biopsy specimen contained large amounts of neutral lipids. Liver biopsy also showed severe but nonspecific fatty changes. Abnormal mitochondrial structure, many electron-dense lysosome-like bodies, and dense, laminate, rounded lipofuscin-like particles were evident.
A thirty-two hour fasting study was performed. During the fasting period the patient had no nausea, cramps, or pigmenturia. However, at thirty-two hours he suddenly had a cardiorespiratory arrest characterized by an absence of cardiac electrical activity. He was successfully resuscitated and intravenously glucose was administered.
At the start of the fast his blood glucose level was 92 mg/dl, but by twenty-four hours it had fallen to 66 mg/dl. Plasma triglyceride levels rose from 66 to 126 mg/dl and free fatty acids increased from 0.1 to 2.0 mEq/liter. Serum SGOT rose from 36 to 1450 I.U./liter, with no increase in creatine phosphokinase or aldolase. Ammonia increased from 40 to 134 ug/dl. The most significant finding, however, was the lack of production of measurable ketone bodies.
During the 11th admission, the diagnosis of carnitine deficiency was considered because of fatty changes in the liver and the lack of production of ketone bodies after twenty-four hours of fasting. At that time the patient's height and weight were normal but his developmental quotient was 40, and he had a variety of neuromuscular abnormalities. A computerized axial tomography (CAT) scan of the brain revealed marked enlargement of both lateral ventricles and of the sulci between the cerebral gyri.
QUESTION: Explain why low levels of ketone bodies is an indication of systemic carnitine deficiency but not myopathic carintine defieciency (limited to muscle tissue).
