Case Study: Increased Serum Creatine Kinase Level in Taxi Driver

This case study presents a 38-year-old white male taxi driver with a history of smoking and combined hyperlipidemia, referred to a lipid clinic. Initial tests revealed elevated serum cholesterol, triglycerides, and an abnormally high serum creatine kinase (CK) level, along with an elevated alanine aminotransferase. Further investigations, including ischemic forearm tests and neurological evaluations like EMG and NCV, led to a diagnosis of chronic partial denervation and a possible heterozygous myoadenylate deaminase (MADA) deficiency, as well as a hereditary sensory motor neuropathy condition. The discussion highlights the importance of CK testing, the ischemic forearm test, and the genetic disorder Charcot-Marie-Tooth (CMT) in diagnosing the patient's condition, emphasizing the need for early detection and specialized treatment. The patient's family history and genetic analysis were also key factors in the diagnosis, ruling out certain genetic mutations and pointing towards a CMT1 diagnosis. The study also provides a review of relevant literature.

Increase of serum creatine kinase level in patients : A case study
A white male taxi driver aged 38 years was a person with a history of smoking 20 pack per
year. He was advised to examine the physiological symptoms leading to combined
hyperlipidemia in a lipid clinic. The lipid clinic gave the results as shown in table 1.
Entry Analyte Result Reference interval
i Serum Cholesterol (250mg/dl) 6.5 mmol/L 3.7-7.0 mmol/L
ii HDL (30.9 mg/dl) 0.8 mmol/L 0.7-1.8 mmol/L
iii Triglycerides (539mg/dL) 6.1mmol/L 1.7 mmol/L
iv Serum creatine kinase 889 U/L 24 –195 U/L
v Alanine aminotransferase 61 U/L 50 U/L
vi Total bilirubin (0.8 mg/dL) 13 mol/L 14 mol/L
vii Alkaline phosphatase 95 U/L 150 U/L
viii -Glutamyltransferase 49 U/L 50 U/L
Table 1: Results of the medical tests
Apart from the above results, other analyses like blood count, anti nuclear antibodies, thyroid
and renal functions, electrophoresis of serum protein, folate, C-reactive protein and serum
vitamin B12 were found to be in the normal range.
Genetic history
The medical history of the patient revealed that his father suffered from myocardial infarction
and died at the age of 55. His mother was incapable of dorsiflexing her feet from the age of

30 due to weakness in the muscles of lower limb. However his maternal half-brother and his
elder brother both aged 38 and 48 respectively were free from any medical concern.
Diagnosis
It was observed from his medical report that his serum creatine kinase (serum CK) level was
abnormally high along with a higher level of alanine aminotransferase than the normal level.
The elevated level of his serum CK was probably due to his hectic physical exercise (Lilleng
et al 2011) so he was advised to reduce his physical activity and re-examine his serum CK
level.
However, the laboratory results indicated that the CK level was still highly elevated at 737
U/L, based on which he was advised for further investigations like plasma carnitile profile,
ischemic forearm tests along with plasma and urinary amino acids test. An increase in
concentration of lactate and ammonia along the borderline was observed in the ischemic
forearm tests while the other two tests (plasma carnitile profile, plasma and urinary amino
acids test) were found to be normal. It was concluded from the ischemic forearm test results
that he might be suffering from heterozygous myoadenylate deaminase (MADA) deficiency.
The patient complained weakness in his legs and was referred to a neurologist who advised
various neurological related tests like hereditary sensory motor neuropathy of the Charcot–
Marie–Tooth (CMT) type, nerve conduction velocity (NCV) studies and electromyography
(EMG) tests. These tests revealed the absence of sural sensory potential but presence of high
arched feet along with chronic partial denervation. He had weakness in evertor muscles and
indicated the absence of many reflexes. The conduction of the motor nerve in the lower limb
was in the demyelinating region as shown by EMG and NCV tests. Thus the patient was
diagnosed with chronic partial denervation by EMG tests. Additionally another clinical

geneticist also suggested a hereditary sensory motor neuropathy condition. A mutation
analysis of genes indicated the absence of mutations in peripheral myelin protein22
(PMP225) genes and myelin protein zero (MPZ) genes.
Discussion
The patient suffered from an abnormally high level of CK activity so can be diagnosed by a
method reported by Kyriakides et al (Kyriakides et al. 2010). They proposed that the causes
for the symptoms like nonmyopathic and nonneuromuscular causes could be eliminated.
They also pointed that the CK activity is not enhanced due to exercise. Again, they proposed
the upper reference limit by studying the hereditary cases of neuromuscular diseases. The
NCV studies (Stojovik, 2016) as well as EMG tests were conducted in the following steps of
the diagnosis.
Creatine kinase (CK)
The creatine kianse (CK) is an enzyme present in the cytoplasm of the muscles and
myofibrils and is used for generating high energy ATP. The enzyme acts as a catalyst for
transferring a phosphate moiety from creatine phosphate to ADP, which in turn synthesizes
the ATP. There are two subunits for the CK enzymes in the cells: muscle (M) and brain (B)
type. Thus CK-MM, CK-BB and CK-MB are three isoenzymes present in cytosol. The CK-
MM is present mainly in the skeletal muscles along with CK-MB in a minor amount. (Baird
et al. 2012) CK is the most prominent test for detecting damages in muscles. Various kinds of
abnormal conditions like malignant hyperthermia, channelopathies, strenuous exercise,
dystrophinopathies, metabolic, infectitious, endocrine and inflammatory myopathies as well
as rhabdomyolysis (Landau et al. 2012) elevates the serum activities of CK-MM. Moreover,
an individual without any muscular disorder may also have elevated CK based on different

factors like exposure to drugs like statins (Mancini et al. 2013) and excessive alcohol or
macro CK. Certain neurological disorders like postpolio syndrome, amyotrophic lateral
sclerosis, hereditary polyneuropathy, someneuropathies along with hereditary spinal muscular
atrophy also lead to the secondary involvement of muscles (Restivo et al. 2012). It becomes
facile for diagnosis of the problem when these medical histories of the patient are taken into
account, but the patients ignore the mild symptoms and treatment is delayed.
Ischemic forearm test
The ischemic forearm test is used for the identification of muscle disorders. (Hogrel et al.
2017) The person is allowed to fast, following which ammonia and lactate synthesized in the
plasma is measured under ischemic state while exercising the forearm. If the ammonia level
is greater than 119 g/dL while that of lactate is greater than 19.8 mg/dL, the response is
normal. This screening test is very significant for detecting debrancher enzyme deficiency,
abnormality in the metabolism of carbohydrate in McArdle disease (Lorenzoni et al. 2018)
as well as MADA deficiency. However, patients suffering from metabolic myopathies and
certain healthy persons fail to exhibit elevated level of ammonia due to the lack of proper
workout during the test.
Charcot-Marie-Tooth (CMT)
The sensory and motor nerves are affected by the genetic disorder called CMT, which is
caused due to gene mutations.( Barreto et al. 2016) The individual suffers from loss in
senses, deformation in foot and distal weakness in his early years due to the classic phenotype
generated by duplication of PMP22 gene. (Hoyle et al. 2015). The CMT is classified as
CMTX, common in males, and CMT4, which belong to the recessive category and rare.
(Amato & Reilly 2011) The CMTX has neurological and pathological similarity to CMT type
1 (CMT 1). The CK activity of the patients affected by CMT was also found to be elevated.
The mutations of the genes are studied in the genetic testing for CMT. (Murphy et al. 2012)

As there is a lack of specific medicine for the treatment of this disorder, surgical and
rehabilation therapy is recommended. The symptoms should be detected in the early years
and treated under proper specialist.
Summary
The patient reported herein was suffering from a genetic disorder called demyelinating
sensorimotor neuropathy as observed from the neurophysiological and clinical investigations.
It has been predicted as autosomal dominant inheritance since two of the generation has been
suffering from the disorder. (Rudnik-Schoneborn et al. 2016) The CMT is not probably X
linked, as both the brother of the patient has been free from the disease indicating that there is
absence of mutation among the PMP 22 and MPZ genes. Hence, these results point to the fact
that he has been affected by the genetic disorder termed as CMT1. His liver related analysis
along with the level of -glutamyltransferase was found to be normal. The secondary
infection due to the effect of CMT on the muscle caused the elevation of alanine
aminotransferase. Thus, the abnormal level of alanine aminotransferase due hepatocellular
injury can be ruled out.
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