Immediately, I thought of my own biopsy reports. Don didn’t know it, but he was talking to another “combo case,” a person with multiple enzyme deficiencies. Thus I knew that Complex I is involved in cellular electron transport and that Don’s 35% residual enzyme activity combined with 54% levels of CPT could add up to myopathy, maybe more. 

Later, after hearing the whole story, I decided his case is “complex” in more ways than one. 

Don was a healthy, active person until his early 30’s when he noticed muscle pain and fatigue during the physical training required for Army Reserve personnel. “At the time I was being treated for a bulging disc and I thought that was part of the problem,” recalls Don. Then in 1985 when Don was nearly 40, pre-op blood tests for gallbladder surgery turned up a high CK (creatine kinase). Subsequent tests revealed his CKs were as changeable as the weather, sometimes high, sometimes lower, but never normal. When Don began having severe pain in his forearms and the muscles turned hard and tight and stiff, his doctor sent him to a rheumatologist.

“That’s when they found out I have ankylosying spondylitis,” says Don. One of several unexpected twists in his story, ankylosying spondylitis (AS) is a form of arthritis too complicated to explain here. Suffice it to say that Don has AS, but that diagnosis still didn’t explain his muscle pain or high CK. 

Next stop: Neurology. After scores of tests, the doctor finally ordered a muscle biopsy, then a second. The reports were essentially identical. Myopathy. Something was wrong, but what? 

Meanwhile, Don was diagnosed with type II diabetes and high blood pressure. The doctors told him he needed to exercise or the diabetes would get worse. But exercise made his muscle pain unbearable. “It was a catch-22,” says Don. 

Predictably, the diabetes did escalate and he began taking insulin every day. “I was in pretty bad shape,” he recalls. “At work a temporary employee came in every day to do all my writing because I couldn’t hold a pen and write. At home I had difficulty shaving and had to use an electric toothbrush because I couldn’t make an up-and-down motion with my hand.”

Then in 1994 Don had a third muscle biopsy and this time the tissue was sent to Dr. Georgirene Vladutiu in Buffalo, NY. When the report came back noting double partial enzyme deficiencies, Don’s nutritional doctor recommended that he see Lyn Howard, M.D., who in turn recommended carnitine supplements. “That’s when things started rolling,” says Don. Within two weeks, he noticed dramatic improvement in muscle function. “I could do at least fifty percent more. It was like a miracle.” 

Though Don is grateful for this comeback, he still has many questions. For example, which disorder is causing which symptoms? Is AS causing his chest pain or his restricted breathing, or is Complex I the culprit? Does each disorder do its own thing or do they interact? “You really can’t sort it out,” says Don. “That’s what drives me nuts.”

More questions surfaced several years ago when Don’s brother Earl developed muscle pain and had a biopsy. The results: CPT levels at 39%, but Earl’s Complex I was normal. Screening both brothers for known mutations in the CPT2 gene simply added to the muscle mystery. Earl, it turns out, carries one copy of the S113L mutation, which accounts for his 39% reduction. But Don doesn’t carry any of the 15 known CPT II mutations. 

So why does Don have a partial CPT deficiency? Is it secondary as Dr. Vladutiu suspects? Why do carnitine supplements produce dramatic improvement in Don’s muscle? Is it treating the reduction in Complex I or CPT or both? Why does his brother get the same dramatic improvement with carnitine when he has one copy of the S113L mutation and no Complex I deficiency at all? Is it possible that both brothers also have a secondary carnitine deficiency?

Given more time and research, eventually some of Don’s dilemma may be understood. But for now, all the biochemical halves in this case mostly add up to a whole lot of questions. 

Combined partial deficiency of muscle carnitine palmitoyltransferase and carnitine with autosomal dominant inheritance
Case history of a mother and son with two partial deficiencies.


To read about other atypical cases of CPT deficiency,  visit Same difference.