Developmental Delays, Do a CK

This page reviews indications for CK testing in children ages 6 months to 5 years. If you see global delay, evaluate for muscle weakness. If you suspect muscle weakness, include a CK as part of your evaluation.

What is a CK (CPK)?

Creatine phosphokinase (CK) is an enzyme found mainly in the skeletal muscle, but also in the heart and brain. Higher-than-expected serum CK indicates leakage of CK through the muscle membrane, and suggests muscle damage either from cardiac or skeletal muscle. In children, elevated CK almost always reflects skeletal muscle damage.

Rationale for CK testing

• A CK is a starting point in the evaluation of a child with motor delay, even if cognitive delay is more of a concern, and helps focus further testing and referrals.
• CK testing is quick and inexpensive.
• CK results can help clinicians differentiate between various disorders that cause weakness, such as distinguishing between central causes of motor delay (normal CK levels) and peripheral causes of motor delay (CK level elevated).
  • There are many peripheral neuromuscular conditions where the CK is always elevated from birth (e.g., in Duchenne and Becker muscular dystrophies, and in some of the congenital muscular dystrophies, and some limb girdle muscular dystrophies) and other conditions where CK is mildly elevated or normal (e,g., spinal muscular atrophy, neuropathies, and congenital myopathies).

Elevated CK warrants prompt referral to neurology. Normal CK does not rule out neuromuscular disease. A mildly elevated CK (1-2x normal) should be followed up. However, please note that a normal CK does not rule out neuromuscular diseases such as spinal muscular atrophy; in this instance genetic testing is required to rule out the disorder.

Use of CK testing

• In children with developmental delay:
  • Evaluate motor milestones in any child who has mild to moderate developmental delay of unknown etiology. (Note that some children with neuromuscular disorders have non-motor developmental delays; for example, delayed language. This may be the feature that first brings them to clinical attention.) If you have any concerns about motor development, include a CK in your screening process. If the CK is high, refer to neurology for consultation.
• In children with motor delay:
  • Order a CK for a child who has unexplained gross motor delay. If the CK is high (≥3 x normal), refer to neurology for consultation.

Findings that should always trigger a CK include:

• Signs of proximal muscle weakness, including:
  • Slipping through hands when held suspended
  • Inability to voluntarily flex neck when supine or head lag when pulled to sit
  • Difficulty rising from floor (including Gowers maneuver, full or modified)
• Loss of motor milestones
• Isolated gross motor delay without other developmental difficulties

Download a pdf of the Surveillance and Referral Aid for Primary Care Providers. This Aid includes assessing weakness by age, clinical evaluation for muscle weakness, guidance on the use of CK testing, and the motor delay algorithm. These materials have been endorsed by the American Academy of Pediatrics.

Referral to a Specialist

Referral to a specialist is indicated when a child fails to meet the motor milestones as described in the “Signs of Weakness by Age” surveillance aid.

Indications of the need for urgent referral to a neurologist:

• Tongue fasciculations
• Loss of or missed motor milestones
• Decrease or slowing of upper and/or lower extremity antigravity movements
• Dysphagia/ failure to thrive combined with paradoxical, diaphragmatic breathing with the appearance of a bell-shaped chest
• CK greater than 3x normal
• Anticipated surgery, due to anesthesia concerns in children with neuromuscular disorders

If a patient has an indication for urgent referral, you should consider direct contact with the neurologist’s office to share concerns, as this may expedite the appointment.

Note: Urine the color of cola/tea, especially with muscle pain: send child immediately to the ER for urgent emergency intervention

When referral to neurology is not urgent, additional referrals to consider:

• Therapy services (PT, OT, speech therapy) may perform detailed motor evaluations, monitor progress over time, and detect the need for additional referrals, but do not make diagnoses. In cases of benign motor delay, these therapies can promote skill acquisition, help parents feel more comfortable working with their children, and foster a greater sense of control.
• Referral to developmental pediatrician or pediatric rehab specialty may be an appropriate first referral for patients who do not have an indication for urgent referral.
• The referring practitioner should continue to evaluate the child’s motor development over time, in partnership with the therapists and other specialists. Referral to a neurologist is warranted for children without improvement after 6 months.
• Know that a specific diagnosis will inform the care given by therapists and other specialists.

Ordering Lab Tests

If you suspect neuromuscular weakness, include a CK as part of your evaluation. However, please note that a normal CK does not rule out neuromuscular diseases such as spinal muscular atrophy; in this instance genetic testing is required to rule out the disorder.

Brain MRI findings:

• Brain MRI is not an initial or routine component of the evaluation of a weak child.
• Abnormal MRI does not exclude a neuromuscular disease.
• Most neuromuscular diseases have normal MRI of brain, but some have characteristic abnormalities.

Elevated transaminases:

Note of warning: If transaminases (AST and ALT) are elevated, check CK. Since AST/ALT can come from muscle or the liver, while CK comes only from muscle, this test will help localize the child’s problem and may prevent unnecessary liver tests.

Interpreting CK results

The amount of CK in the serum is reported in units (U) of enzyme activity per liter (L) of serum. In a healthy adult, the serum CK level varies based on several factors, including gender, race, and activity level. The normal range is generally up to 250 U/L, but may vary by laboratory.

Elevated CK:

Elevated CK warrants a prompt referral to neurology, and in many specialty clinics, an elevated CK level can reduce wait times for consultation. A personal phone call may also be helpful for expediting this process. Grossly elevated CK levels (3,000 to >30,000 U/L) are often seen in Duchenne muscular dystrophy or other muscular dystrophies. During episodes of acute muscle breakdown (i.e., rhabdomyolysis), CK levels can spike dramatically, reaching 50,000 to 200,000 U/L, which is a medical emergency that requires immediate referral to the nearest Emergency Department.

Mildly Elevated CK:

Mildly elevated CK levels (1-2 times normal, typically <500 U/L) should be followed up with a repeat test after several weeks, as it can be temporarily elevated due to self-limited conditions such as recent immunization, muscle trauma, or viral infection. Mildly elevated CK (around 500 U/L) can also occur in neuropathies like Charcot-Marie-Tooth disease or anterior horn cell diseases like spinal muscular atrophy.

Normal CK:

Normal CK levels do not rule out neuromuscular diseases, such as spinal muscular atrophy; in such cases, genetic testing is necessary to rule out the disorder. Additionally, CK levels do not reflect the level of functional impairment. If a child presents with motor delay, referrals to specialists, physical therapy, and early intervention are warranted, even with normal CK levels. Consult with a neurologist if hypotonia is observed.