Elevated Creatine Kinase in a 6-Year-Old Boy

doi:10.1016/j.spen.2017.03.003

Seminars in Pediatric Neurology

Volume 26, July 2018, Pages 46-49

https://doi.org/10.1016/j.spen.2017.03.003 Get rights and content

Paucisymptomatic or asymptomatic but persistently elevated serum creatine kinase is not an uncommon pediatric neurology referral question. The challenge is in promptly identifying etiologies with specific treatments, even if they are rare. The presenting features for a child or adolescent with juvenile-onset Pompe disease (JOPD) can be nonspecific and heterogeneous. Clinical manifestations can appear at any age after 2 years and before adulthood, with insidious onset of symptoms related to slowly progressive skeletal or respiratory muscle weakness. This reported case highlights the importance of screening for JOPD in children with “hyper-CK-emia.” Dried blood spot measuring acid α-glucosidase enzyme activity is reliable, rapid, noninvasive, and inexpensive, allowing early diagnosis. Diagnosis of JOPD is important as enzyme replacement therapy with alglucosidase alpha, an intravenous recombinant α-glucosidase, is available, and early treatment improves muscle function, quality of life, and long-term survival.

Section snippets

Case

A 6-year-old boy was referred for an outpatient pediatric neurology evaluation following detection of mildly elevated serum creatine kinase (sCK) at 908 and 667 IU/L (normal reference range: 40-240 IU/L) on 2 occasions, with elevated alanine and aspartate transaminases, in the absence of identifiable liver disease. Investigations had been performed for nonspecific intermittent abdominal pain over the previous 2 years.

At presentation, a history of intermittent activity intolerance and myalgia

Discussion

CK is a muscle enzyme involved in converting phosphocreatine and adenosine diphosphate to creatine and adenosine triphosphate to generate energy crucial for muscle function. When there is muscle injury and sarcolemmal disruption, leakage of CK into the blood stream can occur, resulting in an elevation of sCK.

An elevation in sCK greater than 1.5 times normal is considered abnormal1, 2 and can be associated with no symptoms or minor symptoms such as nonspecific cramps, myalgia, or fatigue. There

Conclusion

JOPD, a rare inherited progressive myopathy, can present with insidious onset of symptoms in childhood, typically resulting from progressive skeletal and respiratory muscle weakness. The presence of nonspecific but persistent elevation of sCK should prompt consideration of screening for GAA enzyme activity on DBS. Unlike many other inherited myopathies, disease-specific ERT is available for JOPD. Early diagnosis is crucial as treatment significantly improves these patients’ long-term outcomes.

References (33)

M. Dasouki et al.
Pompe disease: Literature review and case series
Neurol Clin
(2014)
N.A. van der Beek et al.
Rate of disease progression during long-term follow-up of patients with late-onset Pompe disease
Neuromuscul Disord
(2009)
P.S. Kishnani et al.
Pompe disease diagnosis and management guideline
Eur J Neurol Genet Med
(2006)
B. Winchester et al.
Methods for a prompt and reliable laboratory diagnosis of Pompe disease: Report from an international consensus meeting
Mol Genet Metab
(2008)
H. Kallwass et al.
Rapid diagnosis of late-onset Pompe disease by fluorometric assay of alpha-glucosidase activities in dried blood spots
Mol Genet Metab
(2007)
N.A. Chamoles et al.
Glycogen storage disease type II: Enzymatic screening in dried blood spots on filter paper
Clin Chim Acta
(2004)
U. Mellies et al.
Pompe disease: A neuromuscular disease with respiratory muscle involvement
Respir Med
(2009)
L.E. van den Berg et al.
Low bone mass in Pompe disease: Muscular strength as a predictor of bone mineral density
Bone
(2010)
S. Moghadam-Kia et al.
Approach to asymptomatic creatine kinase elevation
Cleve Clin J Med
(2016)
R.A. Nardin et al.
Effect of newly proposed CK reference limits on neuromuscular diagnosis
Muscle Nerve
(2009)

T. Kyriakides et al.

EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia

Eur J Neurol

(2010)

E.K. Chan et al.

A diagnostic approach to recurrent myalgia and rhabdomyolysis in children

Arch Dis Child

(2015)

N.J. Silvestri et al.

Asymptomatic/pauci-symptomatic creatine kinase elevations (hyperckemia)

Muscle Nerve

(2013)

C. Fernandez et al.

Diagnostic evaluation of clinically normal subjects with chronic hyperCKemia

Neurology

(2006)

The National Organization for Rare Disorders. The physician’s guide to Pompe disease. 2013. Available at:...

E.J. Cupler et al.

Consensus treatment recommendations for late-onset Pompe disease

Muscle Nerve

(2012)

Cited by (3)

Is it Pompe Disease? Australian diagnostic considerations
2020, Neuromuscular Disorders
Citation Excerpt :
CK elevations are universally observed in IOPD and are seen in the majority of patients with LOPD, with levels ranging from 1.5 to 15 times the upper limit of normal [8]. Measuring GAA activity in DBS aids the early identification of juvenile-onset Pompe Disease (JOPD) in pauci-symptomatic or asymptomatic children with persistently elevated CK levels [32]. HyperCKaemia is usually mild and sometimes the only manifestation in asymptomatic patients [22].
Pompe Disease is a spectrum disorder with an evolving phenotype in which diagnostic delay is common. Contributing factors include the rarity of the disorder, its wide clinical spectrum, signs and symptoms that overlap with those of other neuromuscular disorders, variable diagnostic approaches, lack of awareness of the clinical manifestations and difficulties in completing the diagnostic inventory. International updates and recommendations have been published providing diagnostic guidelines and management criteria. However, questions remain in the Australian setting. A panel (two neurologists, one clinical geneticist) reviewed the literature, examined clinical questions of relevance to the Australian setting, and developed a framework for the guidance. A wider panel, comprising the initial panel plus eight additional members, critiqued the framework and contributed clinical guidance within the scope of their respective areas of clinical expertise. The resultant expert consensus recommendations build on currently available data to propose an appropriate management framework incorporating the diagnosis, classification, therapeutic approach, multidisciplinary care, and on-going monitoring of patients with Pompe Disease in the Australian setting. It is hoped that diagnostic delay can be reduced with appropriate recourse to evidence-based insights and practical advice on diagnosis and management tailored to the Australian setting.
HyperCKemia associated with acupuncture: a case report and review of the literature
2022, BMC Complementary Medicine and Therapies
Significance of Asymptomatic Hyper Creatine-Kinase Emia
2019, Journal of Clinical Neuromuscular Disease

View full text

Elevated Creatine Kinase in a 6-Year-Old Boy

Section snippets

Case

Discussion

Conclusion

Neurol Clin

Neuromuscul Disord

Eur J Neurol Genet Med

Mol Genet Metab

Mol Genet Metab

Clin Chim Acta

Respir Med

Bone

Approach to asymptomatic creatine kinase elevation

Cleve Clin J Med

Effect of newly proposed CK reference limits on neuromuscular diagnosis

Muscle Nerve

EFNS guidelines on the diagnostic approach to pauci- or asymptomatic hyperCKemia

Eur J Neurol

A diagnostic approach to recurrent myalgia and rhabdomyolysis in children

Arch Dis Child

Asymptomatic/pauci-symptomatic creatine kinase elevations (hyperckemia)

Muscle Nerve

Diagnostic evaluation of clinically normal subjects with chronic hyperCKemia

Neurology

Consensus treatment recommendations for late-onset Pompe disease

Muscle Nerve