LETTERS TO THE EDITOR
HYPERTRIGLYCERIDEMIA IN CARNlTlNE PALMITYL TRANSFERASE DEFICIENCY: LIPID PROFILE AND TREATMENT WITH MEDIUM CHAIN TRIGLYCERIDES* A patient with carnitine palmityl transferase (CPT) deficiency was placed on a low-fat diet of 40 to 50 grams of fat with total caloric intake of 1800 to 2000 calories per day (20% protein, 55% carbohydrates, 25% fat). A.M. fasting and p.m. 2-hour postprandial lipid profile, including total serum cholesterol, triglycerides, and HDL, LDL, and VLDL cholesterol levels were measured. The patient was then started on 60 g medium chain triglyceride oil per day with other daily dietary fats reduced to 25 g. T he diet, therefore, contained 37% fat (27% medium chain and 10% long chain fatty
acids). After 4 weeks, fasting and 2-hour postprandial lipid profile was repeated over a 3-day period. T he only abnormality observed in the lipid profile was an increase in triglyceride levels, with the postprandial levels being higher than the fasting levels (Table 1). Serum triglycerides were substantially reduced in both fasting (27% reduction) and postprandial (46% reduction) samples by the medium chain triglyceride (MCT) diet. Plasma free fatty acids were normal. Isoelectric focusing of the protein moiety of VLDL revealed that the patient had an APO E, phenotype." A precise explanation for the high incidence of hypertriglyceridemia in CPT deficiency has not been elucidated, nor has treatment of this metabolic abnormality previously been undertaken. Of the reported patients with CPT deficiency (including the one in this
Table 1 A. Fasting vs postprandial serum triglycerides. Before MCT diet
Triglycerides* (mgW
After MCT diet
Fasting (F)
Postprandial (PP)
Fasting (F)
Postprandial (PP)
Day 1
307
495
201
217
2 3
31 0 235
377 433
169 246
230 257
B. Lipidilipoprotein profiles
Total cholesterolt Tnglycerides* LDL cholesterol* VLDL cholesterol HDL cholesterol§
Without MCT diet
With MCT diet
186 269 92 54 40
204 203 107 53 44
200 35- 160 130 5-25 27-58
'Triglycerides were measured using the method described by Lipid Research Clinics Manual Normal range 35-160 mgldL
jrotal and lipoprotein cholesterol and triglycerides were measured according to the method described by the Lipid Research Clintcs Manual #LDL cholesterol was e/ther calculated by using the Friedwald formula' or obtained by Itpoprotem ultracentrtfugafion as described previously 5 H D L was isolated by precipitation of LDL and V L D L with sodium phosphotungstate as described previously
''
676
Letters to the Editor
MUSCLE & NERVE
I'
July 1991
report), 8 of 40 had elevated triglycerides."-"8 Many investigators have noted a rise in plasma triglycerides and free fatty acids in CPT patients during but this was not observed in our patient. Few previous studies have been reported in which medium chain triglycerides have been given to patients with CPT defi~iency.'.~.'Some investigators found improved ketogenesis with medium chain triglyceride feeding suggesting that short chain acylcarnitine transferase activity is intact in CPT d e f i ~ i e n c y . ' ~ ' ~ ~ It is possible that the hypertriglyceridemia in this patient is an associated defect rather than a direct consequence of impaired fatty acid utilization. Endogenous hypertriglyceridemia is a relatively common form of dyslipidemia in the general population. Favoring this hypothesis is the fact that the changes in triglyceride levels associated with the fasting and postprandial state are similar to those observed in dyslipidemic individuals. It is also possible that medium-chain triglycerides do not constitute an ideal substrate for triglyceride production and that VLDL secretion is subsequently impaired. Alternatively, these patients may have an impaired clearance of triglyceride-rich lipoprotein remnants that would be ameliorated by avoiding chylomicron formation. Because the patient had an APO E:, phenotype, the hypertriglyceridemia observed was not likely to be due to impaired removal of triglyceride-rich lipoprotein remnants. Perhaps further study of chylomicron formation and clearance in these patients is warranted. We have demonstrated that a change from a low-fat diet to a medium-chain triglyceride diet resulted in lowered triglyceride levels in a hypertriglyceridemic patient with CPT deficiency. I t is not known whether the patient's risks of myoglobinuria or atherosclerosis would be lowered by long-term treatment. Thomas F. Scott, MD Division of Neurology Department of Internal Medicine Medical College of Pennsylvania Pittsburgh, Pennsylvania 15212 Maria Virella-Lopes, MD Department of Internal Medicine Medical University of South Carolina Charleston, South Carolina 29425 Michael J. Malone Department of Neurology Veterans Administration Medical Center Charleston, South Carolina 29425 1. Angelini C, Freddo L, Battistella P, Bresolin N , PieroboiiBormioli S, Armani M, Vergani L: Carnitine palmityltransferase deficiency: Clinical variability, carrier detection, and autosomal recessive inheritance. Neul-ology 198 1 ; 3 1 :883-
886.
2. Bank WJ, DiMauro S, Bonilla E, Capuzzi DM, Rowlantl LP: A disorder of muscle lipid metabolism and myoglobinuria. N Engl J Med 3975;292:443-449. 3 . Bertorini T, Yeh YY, Trevisan C, Stadlati E, Sabsesin S, DiMauro S: Carnitine palmityltransferase deficiency: Myo-
Letters to the Editor
4.
5.
6.
7.
8.
9. 10.
I I. 12.
globiniu-ia and respiratory failure. NCILVOIOAT 1980;30:269270. Carroll JE, Brooke MH, DeVivo DC, Kaiser K K , Hagberg j M : Biochemical and physiologic consequences of carnitine palmityltransferase deficiency. Mz~.sclrN P ~ W 1978; 1: 103109. Dillonato S, Castiglione A, Rimoltli M, et al: t-letei-ogeneity of carnitine-palmitotraiisferase deficiency. J N~u?(JESri 1981;50:2O7-2 15. DiDonato S, Cornelio F, Pacini L, Peluchetti D, Rinioldi M, Spreafico S: Muscle cartiitine-palmityltralisferase deficiency: Report of a case with enzyme deficiency in cultured fibroblasts. AWLNrul-ol 1978;4:465-467. Friedewald W I - , Levy RJ, Fretlerickson DS: Estimation o f concentration of low-density lipoprotein cholesterol in plasma withour the use of the preparative centrifuge. CliIc Chrm 1972; 18:499-509. Hostetler KY, Hoppel CL, Romine JS, Sipe JC, Gross SR. Higginbottom PA: Partial deficiency of' muscle carnitine palmityltransferase with normal ketone production. N Eugl 1 M r d 1978 ;298 :553- 557. Lipid Research Clinics Program, in iMa?zucil uf Lipid (@erafioirs, V O / . I , Lzjlid and L Z p ( ~ p ~ l rAimlysis, i?~ National Heart and Lung Institute, 1973, Publ. No (NIH) 75-628. Lopes-Virella MF, Sherer GK, Lees AM, Wohltmann t i , Mayfield R, et al: Surf'ace binding, internalization and degradation by cultured human fibroblasts of low-density lipopr-otein isolated from Type 1 (insulin-depenclent) diabetic patients: Changes with metabolic control. L)iuhetologia 1982;22:430-436. Lor)es-Virella MF, Stone P. Ellis S, Colwell 1A: Cholesterol determination in high density lipoproteins separated by three different methotls. C l i i i Clwm 3977;23:882-884. Warniick G R , Mayfield C, Alber J J , Hazard WK: Gel isoelectric focusing method for specific diagnosis of Familial hyperlipoproteinetiiia type 3. Clzu Ckrm 1979;25:279-284.
SPARING OF THE FLEXOR CARPI ULNARIS IN ULNAR NEUROPATHY AT THE ELBOW We found the article by Campbell et all to be interesting and informative. T h e use of both cadavers and clinical examination in treating the subject matter of UNE was a good way to blend existing anatomical findings with modern-day electrodiagnostic muscle testing techniques. In the discussion section the authors referred to two aspects of muscle dysfunction: ( I ) "Dying B a c k theory and (2) the topography of a nerve. Even though the authors discussed these two ideas, they failed to mention an integral aspect of nerve topography which deals with physiology of the nerve cell, that of axoplasmic flow and axonal transport of nerve cell substances. "Substances that originate in the body of a nerve cell are indeed distributed along the axon and delivered to the axon's terminals by passage through the lumen, or bore of a fiber, and these substances play a vital role in neural activity" (Schwartz'). T h e omission of this aspect in no way lessens the significance of their research; however, it could have been used to substantiate the authors' position.
MUSCLE & NERVE
July 1991
677
We feel the authors have sufficiently addressed their hypothesis. A possible addition to this study would be to follow u p with the clinical subjects upon their demise and perform a dissection of the involved elbow to determine the level of the flexor carpi ulnaris nerve branching. This information could be used in correlation with the electrodiagnostic tests previously performed on these subjects. This correlation could either more soundly demonstrate the truth of their hypotheses, or reveal another possible variable. As far as current clinical studies are concerned, to fully appreciate the complexity of this sparing effect, more experimentation should be done using test animals as subjects. Using measured and controlled compression of nerve bundles and electrodiagnostic analysis of muscle tone and function, a more complete picture might appear to explain this unique “sparing” phenomenon. William R. McCoy, AS, BS Steve L. Perry, AS Cleveland Chiropractic College Kansas City, MO 64131 1. Campbell William W. et al: Sparing of the flexor carpi ulnaris in ulnar neuropathy at the elbow. Muscle Nerve 1989; 12:965-967.
678
Letters to the Editor
2. Schwartz JH: The transport of substances in nerve cell. Scz A m 1980;4:152-171.
SPARING OF THE FLEXOR CARPI ULNARIS IN ULNAR NEUROPATHY AT THE ELBOW: A REPLY We appreciate the interest that Mr. McCoy and Mr. Perry have shown in our article “Sparing of the Flexor Carpi Ulnaris in Ulnar Neuropathy at the Elbow.” We agree that the concept of axoplasmic flow is important in understanding neuropathies. If compressive neuropathies d o indeed impair function in the most distal twigs, a controversial notion, it most likely happens through some interference with axonal transport. To follow all our patients u p with post mortem elbow dissections would indeed be an admirable pursuit of knowledge. William W. Campbell, MD Medical College of Virginia Richmond, VA 23298
MUSCLE & NERVE
July 1991
HYPERTRIGLYCERIDEMIA IN CARNlTlNE PALMITYL TRANSFERASE DEFICIENCY: LIPID PROFILE AND TREATMENT WITH MEDIUM CHAIN TRIGLYCERIDES* A patient with carnitine palmityl transferase (CPT) deficiency was placed on a low-fat diet of 40 to 50 grams of fat with total caloric intake of 1800 to 2000 calories per day (20% protein, 55% carbohydrates, 25% fat). A.M. fasting and p.m. 2-hour postprandial lipid profile, including total serum cholesterol, triglycerides, and HDL, LDL, and VLDL cholesterol levels were measured. The patient was then started on 60 g medium chain triglyceride oil per day with other daily dietary fats reduced to 25 g. T he diet, therefore, contained 37% fat (27% medium chain and 10% long chain fatty
acids). After 4 weeks, fasting and 2-hour postprandial lipid profile was repeated over a 3-day period. T he only abnormality observed in the lipid profile was an increase in triglyceride levels, with the postprandial levels being higher than the fasting levels (Table 1). Serum triglycerides were substantially reduced in both fasting (27% reduction) and postprandial (46% reduction) samples by the medium chain triglyceride (MCT) diet. Plasma free fatty acids were normal. Isoelectric focusing of the protein moiety of VLDL revealed that the patient had an APO E, phenotype." A precise explanation for the high incidence of hypertriglyceridemia in CPT deficiency has not been elucidated, nor has treatment of this metabolic abnormality previously been undertaken. Of the reported patients with CPT deficiency (including the one in this
Table 1 A. Fasting vs postprandial serum triglycerides. Before MCT diet
Triglycerides* (mgW
After MCT diet
Fasting (F)
Postprandial (PP)
Fasting (F)
Postprandial (PP)
Day 1
307
495
201
217
2 3
31 0 235
377 433
169 246
230 257
B. Lipidilipoprotein profiles
Total cholesterolt Tnglycerides* LDL cholesterol* VLDL cholesterol HDL cholesterol§
Without MCT diet
With MCT diet
186 269 92 54 40
204 203 107 53 44
200 35- 160 130 5-25 27-58
'Triglycerides were measured using the method described by Lipid Research Clinics Manual Normal range 35-160 mgldL
jrotal and lipoprotein cholesterol and triglycerides were measured according to the method described by the Lipid Research Clintcs Manual #LDL cholesterol was e/ther calculated by using the Friedwald formula' or obtained by Itpoprotem ultracentrtfugafion as described previously 5 H D L was isolated by precipitation of LDL and V L D L with sodium phosphotungstate as described previously
''
676
Letters to the Editor
MUSCLE & NERVE
I'
July 1991
report), 8 of 40 had elevated triglycerides."-"8 Many investigators have noted a rise in plasma triglycerides and free fatty acids in CPT patients during but this was not observed in our patient. Few previous studies have been reported in which medium chain triglycerides have been given to patients with CPT defi~iency.'.~.'Some investigators found improved ketogenesis with medium chain triglyceride feeding suggesting that short chain acylcarnitine transferase activity is intact in CPT d e f i ~ i e n c y . ' ~ ' ~ ~ It is possible that the hypertriglyceridemia in this patient is an associated defect rather than a direct consequence of impaired fatty acid utilization. Endogenous hypertriglyceridemia is a relatively common form of dyslipidemia in the general population. Favoring this hypothesis is the fact that the changes in triglyceride levels associated with the fasting and postprandial state are similar to those observed in dyslipidemic individuals. It is also possible that medium-chain triglycerides do not constitute an ideal substrate for triglyceride production and that VLDL secretion is subsequently impaired. Alternatively, these patients may have an impaired clearance of triglyceride-rich lipoprotein remnants that would be ameliorated by avoiding chylomicron formation. Because the patient had an APO E:, phenotype, the hypertriglyceridemia observed was not likely to be due to impaired removal of triglyceride-rich lipoprotein remnants. Perhaps further study of chylomicron formation and clearance in these patients is warranted. We have demonstrated that a change from a low-fat diet to a medium-chain triglyceride diet resulted in lowered triglyceride levels in a hypertriglyceridemic patient with CPT deficiency. I t is not known whether the patient's risks of myoglobinuria or atherosclerosis would be lowered by long-term treatment. Thomas F. Scott, MD Division of Neurology Department of Internal Medicine Medical College of Pennsylvania Pittsburgh, Pennsylvania 15212 Maria Virella-Lopes, MD Department of Internal Medicine Medical University of South Carolina Charleston, South Carolina 29425 Michael J. Malone Department of Neurology Veterans Administration Medical Center Charleston, South Carolina 29425 1. Angelini C, Freddo L, Battistella P, Bresolin N , PieroboiiBormioli S, Armani M, Vergani L: Carnitine palmityltransferase deficiency: Clinical variability, carrier detection, and autosomal recessive inheritance. Neul-ology 198 1 ; 3 1 :883-
886.
2. Bank WJ, DiMauro S, Bonilla E, Capuzzi DM, Rowlantl LP: A disorder of muscle lipid metabolism and myoglobinuria. N Engl J Med 3975;292:443-449. 3 . Bertorini T, Yeh YY, Trevisan C, Stadlati E, Sabsesin S, DiMauro S: Carnitine palmityltransferase deficiency: Myo-
Letters to the Editor
4.
5.
6.
7.
8.
9. 10.
I I. 12.
globiniu-ia and respiratory failure. NCILVOIOAT 1980;30:269270. Carroll JE, Brooke MH, DeVivo DC, Kaiser K K , Hagberg j M : Biochemical and physiologic consequences of carnitine palmityltransferase deficiency. Mz~.sclrN P ~ W 1978; 1: 103109. Dillonato S, Castiglione A, Rimoltli M, et al: t-letei-ogeneity of carnitine-palmitotraiisferase deficiency. J N~u?(JESri 1981;50:2O7-2 15. DiDonato S, Cornelio F, Pacini L, Peluchetti D, Rinioldi M, Spreafico S: Muscle cartiitine-palmityltralisferase deficiency: Report of a case with enzyme deficiency in cultured fibroblasts. AWLNrul-ol 1978;4:465-467. Friedewald W I - , Levy RJ, Fretlerickson DS: Estimation o f concentration of low-density lipoprotein cholesterol in plasma withour the use of the preparative centrifuge. CliIc Chrm 1972; 18:499-509. Hostetler KY, Hoppel CL, Romine JS, Sipe JC, Gross SR. Higginbottom PA: Partial deficiency of' muscle carnitine palmityltransferase with normal ketone production. N Eugl 1 M r d 1978 ;298 :553- 557. Lipid Research Clinics Program, in iMa?zucil uf Lipid (@erafioirs, V O / . I , Lzjlid and L Z p ( ~ p ~ l rAimlysis, i?~ National Heart and Lung Institute, 1973, Publ. No (NIH) 75-628. Lopes-Virella MF, Sherer GK, Lees AM, Wohltmann t i , Mayfield R, et al: Surf'ace binding, internalization and degradation by cultured human fibroblasts of low-density lipopr-otein isolated from Type 1 (insulin-depenclent) diabetic patients: Changes with metabolic control. L)iuhetologia 1982;22:430-436. Lor)es-Virella MF, Stone P. Ellis S, Colwell 1A: Cholesterol determination in high density lipoproteins separated by three different methotls. C l i i i Clwm 3977;23:882-884. Warniick G R , Mayfield C, Alber J J , Hazard WK: Gel isoelectric focusing method for specific diagnosis of Familial hyperlipoproteinetiiia type 3. Clzu Ckrm 1979;25:279-284.
SPARING OF THE FLEXOR CARPI ULNARIS IN ULNAR NEUROPATHY AT THE ELBOW We found the article by Campbell et all to be interesting and informative. T h e use of both cadavers and clinical examination in treating the subject matter of UNE was a good way to blend existing anatomical findings with modern-day electrodiagnostic muscle testing techniques. In the discussion section the authors referred to two aspects of muscle dysfunction: ( I ) "Dying B a c k theory and (2) the topography of a nerve. Even though the authors discussed these two ideas, they failed to mention an integral aspect of nerve topography which deals with physiology of the nerve cell, that of axoplasmic flow and axonal transport of nerve cell substances. "Substances that originate in the body of a nerve cell are indeed distributed along the axon and delivered to the axon's terminals by passage through the lumen, or bore of a fiber, and these substances play a vital role in neural activity" (Schwartz'). T h e omission of this aspect in no way lessens the significance of their research; however, it could have been used to substantiate the authors' position.
MUSCLE & NERVE
July 1991
677
We feel the authors have sufficiently addressed their hypothesis. A possible addition to this study would be to follow u p with the clinical subjects upon their demise and perform a dissection of the involved elbow to determine the level of the flexor carpi ulnaris nerve branching. This information could be used in correlation with the electrodiagnostic tests previously performed on these subjects. This correlation could either more soundly demonstrate the truth of their hypotheses, or reveal another possible variable. As far as current clinical studies are concerned, to fully appreciate the complexity of this sparing effect, more experimentation should be done using test animals as subjects. Using measured and controlled compression of nerve bundles and electrodiagnostic analysis of muscle tone and function, a more complete picture might appear to explain this unique “sparing” phenomenon. William R. McCoy, AS, BS Steve L. Perry, AS Cleveland Chiropractic College Kansas City, MO 64131 1. Campbell William W. et al: Sparing of the flexor carpi ulnaris in ulnar neuropathy at the elbow. Muscle Nerve 1989; 12:965-967.
678
Letters to the Editor
2. Schwartz JH: The transport of substances in nerve cell. Scz A m 1980;4:152-171.
SPARING OF THE FLEXOR CARPI ULNARIS IN ULNAR NEUROPATHY AT THE ELBOW: A REPLY We appreciate the interest that Mr. McCoy and Mr. Perry have shown in our article “Sparing of the Flexor Carpi Ulnaris in Ulnar Neuropathy at the Elbow.” We agree that the concept of axoplasmic flow is important in understanding neuropathies. If compressive neuropathies d o indeed impair function in the most distal twigs, a controversial notion, it most likely happens through some interference with axonal transport. To follow all our patients u p with post mortem elbow dissections would indeed be an admirable pursuit of knowledge. William W. Campbell, MD Medical College of Virginia Richmond, VA 23298
MUSCLE & NERVE
July 1991
