A 27 year old male presents to ED with myalgia and dark urine.

His U&E are through the shoot! Cr 765!!! He’s not passed much urine either.

He’s been unwell for a few days with flu-like symptoms. His inflammatory markers are slightly raised and he is given IV fluids. Gas was ok on this occasion and no concerns over K+.

Luckily, the AKI protocol is pretty decent in this DGH and a CK was sent by the ED SHO. This returns at 78 408.

What are we thinking here:

The medical SHO is interested and asks if he’s ever had dark urine before.

“Yes doc! After I’d been to the gym that one time. Never went back.”

The medical SHO once happened upon a metabolic medicine clinic by accident. He remembers something about carnitine.

Carnitine palmitoyltransferase 2 (CPT2) deficiency is a rare autosomal recessive disorder but is actually the most common form of metabolic myopathy. It affects 1-9 people in 100 000 but likely under diagnosed.

CPT2 plays an essential role in transporting long-chain fatty acids from the cytosol to the mitochondrial matrix. It’s absence or reduced function leads to inadequate fatty acid oxidation and accumulation of long chain acylcarnitines.

This causes lysis of muscle cells and release of myoglobin which the kidneys really don’t like.

Interestingly, different mutations in CPT2 can cause distinct conditions. Biallelic loss-of-function variants (frameshift, nonsense and some missense) cause a lethal neonatal disorder with hypoketotic hypoglycaemia.

Some biallelic missense variants can reduce enzyme function (aka hypomorphic) and lead to adult-onset myopathy which is often exercise-induced but any catabolic state (such as intercurrent infection) can bring about rhabdomyolysis.

There is also an infantile encephalopathic form caused by some rare missense mutations. Just to add to the confusion.

Over 60% of adult-onset CPT2 in Europeans is caused by the same variant, p.Ser113Leu (substitution of Serine for Leucine at amino acid residue 113). This variant reduces stability of the protein although it is still functional.

Diagnosis can be achieved by checking plasma acylcarnitines, which will show an elevation of C12 to C18 acylcarnitines.

But molecular confirmation is usually by a next generation sequencing panel for metabolic myopathy (so will include other rarer causes). CPT2 enzyme activity can also be measured on muscle tissue from biopsy (molecular phenotyping).

Treatment in the acute setting involves rigorous fluid replacement and dialysis if necessary. Attempts must be made to avoid at catabolic state as far as possible.

Prevention of rhabdomyolysis by avoiding triggers and a diet low in long-chain fatty acids and supplement with medium chain triglycerides and carnitine. Dietetic support must not be understated.

Don’t be fooled by age as patients have been known to present in their 60s. Maybe they have a history of exercise intolerance?

CPT2 deficiency unfortunately remains under diagnosed. https://www.frontiersin.org/articles/10.3389/fgene.2019.00497/full