Fundamental differences



Fundamental differences
--Georgirene D. Vladutiu, Ph.D.

As we begin the discussion of carnitine palmitoyltransferase (CPT) deficiency disorders, it is important to get the nomenclature straight right from the start.

“CPT” refers to 3 distinct enzymes.

L-CPT I is found predominantly in liver.

M-CPT I is found predominantly in muscle.

CPT II is found in all cells studied thus far.

The CPT I isoforms and CPT II are distinct enzymes encoded by different genes and residing on different membrane surfaces in mitochondria.

The gene for L-CPT I is called CPT1A.

The gene for M-CPT I is called CPT1B.

The gene for CPT II is CPT2.

CPT deficiency is a group of disorders collectively representing defects in either CPT I or CPT II.

The CPT enzymes work together with other enzymes to transport lipid (fatty acids) into mitochondria so they can be used to make energy known as ATP. If one of the enzymes is defective, then the transport system is impaired and energy production is compromised.

The most common disorder of CPT is the “adult onset“ form of CPT II deficiency. It is characterized by pain and stiffness usually (but not always) followed by the appearance of dark-colored urine (myoglobinuria) occurring after:

vigorous exercise

fasting

exposure to extremes in temperature

viral infection

anesthesia

sleep deprivation

or other triggers.

There are two rare infantile forms of CPT II deficiency:

a fatal neonatal form with hypoglycemia and the involvement of many organ systems.

a severe form involving liver, heart, and muscle which may occur after the neonatal period.

L-CPT I deficiency is an infantile disorder affecting liver function.

M-CPT I deficiency is a muscle disorder that has not yet been observed in humans.

The diagnosis of these disorders relies first on recognizing the clinical symptoms, then on performing enzyme analysis and, most recently, mutation analysis.

For information about CPT II deficiency mutation screening available at the Robert Guthrie Biochemical Genetics Laboratory in Buffalo, NY, visit On the spot.

Dr. Vladutiu is Associate Professor of Pediatrics, Neurology and Pathology at the State University of New York at Buffalo School of Medicine. The recipient of an MDA research grant, her recent work has focused on molecular genetic studies of carnitine palmitoyltransferase deficiencies.

CPT2 refers to the gene that encodes the CPT II enzyme. CPT II refers to the enzyme. Therefore when referring to the deficiency, it is correct to say CPT II deficiency.

CPT2 always appears in italics, whereas CPT II does not.

References:
Britton CH et al. Genomics 40:209-211, 1997
Taroni F and Uziel G Curr Opin Neurol 9:477-485, 1996

Related links:
Matter over Mind: The Realities of a Common Muscle Disease FOD newsletter article about CPT II deficiency by Dr. Vladutiu.

Features of carnitine palmitoyltransferase type I deficiency

Carnitine palmitoyltransferase I deficiency

A case history.

For more from Dr. Vladutiu about CPT deficiency, visit When is CPT II deficiency really CPT+?

For a step-by-step explanation of enzymes and how they work, visit The virtual enzyme.

For more about a case of L-CPT I deficiency, visit Significant others.

Not only does age of onset vary in CPT II deficiency but also there has been a wide range of symptoms reported among affected individuals. Because some individuals remain asymptomatic until triggered, there are likely to be many people with the disorder who are completely unaware of its existence. The disorder has even been called "benign" in some scientific reports, which could not be farther from the truth for individuals who have experienced life-threatening kidney failure following a severe episode of rhabdomyolysis.

--G. D. Vladutiu, Ph.D.