Carnitine palmitoyltransferase 2 (CPT2) deficiency is a disorder of fatty acid metabolism. Individuals diagnosed with this disease early on tend to experience more severe outcomes. However, this disease can be detected via tandem mass spectrometry, meaning that early diagnosis and treatment are possible. 

CPT 2 deficiency was a primary target of the Maritime Newborn Screening Program, which was initiated in 2005. Out of 220,000 newborns screened, only 1 positive case was identified, which is described in the case study below. 

Read more about long chain fatty acid oxidation disorder etiology 

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Should there be greater advocacy for CPT 2 deficiency to be included in more newborn screening programs, considering the rarity of this disease? 

“On the whole, [fatty acid oxidation disorders] are regarded as good targets for newborn screening because affected children usually appear to be healthy, and the onset of catastrophic symptoms can be prevented by frequent feeding and, during sick days, by intravenous administration of glucose,” Tajima and colleagues opined in the Journal of Human Genetics. 

Disease Course of CPT 2 Deficiency 

In the International Journal of Neonatal Screening, Mador-House and colleagues presented the case of the single infant who was identified positive for CPT 2 deficiency from the Maritime Newborn Screening Program. The case report, as presented, details a female infant who was born via vaginal delivery. She was born at 40 weeks and weighed 3,374 g. 

On her 8th day of life, expanded newborn screening identified the child as being at risk for CPT 2 deficiency or carnitine-acylcarnitine translocase (CACT) deficiency. The results were based on a dried blood spot test collected 25 hours after birth. 

“Plasma (collected at 9 days of age) carnitine/acylcarnitine profile analysis was performed in the Department of Pediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, Canada, and it confirmed elevations in long chain acylcarnitines consistent with CPT 2 deficiency,” Mador-House and colleagues wrote. 

On her 9th day of life, the child underwent a physical examination, which was normal; more specifically, she had normal cardiac parameters, normal tone, and hepatosplenomegaly was absent. However, her creatine phosphokinase levels were mildly elevated. 

Her physicians educated the child’s parents on best care practices: avoid fasting for longer than 3 to 4 hours and to bring the child to an emergency hospital should she ever present with an illness, lethargy, seizures, or an inability to feed every 3 hours. 

Upon discovering that the child’s residual carnitine palmitoyltransferase 2 enzyme activity was 5% of normal and that her genetic testing for CACT was negative, a diagnosis of CPT 2 deficiency was confirmed. 

“The laboratory director who issued the CPT 2 report suggested that her low residual enzyme activity placed her within the severe infantile hepato-cardio-muscular spectrum of the CPT 2 disorder,” Mador-House et al wrote. 

During her first 5 years of life, the child had around 15 hospital admissions due to decreased feeding/vomiting. In most cases, her CPK levels were increased, typically in the 1000 s μ/L range. The patient was typically administered D10 IV fluids and discharged when her CPK levels fall below 300 μ/L, and her muscle pain is resolved. 

At home, the patient was managed with dietary control and supplements, such as being on a low-fat diet, avoidance of fasting, carnitine supplementation, and walnut oil. The parents of the child were also advised to avoid metabolic stressors such as infection, as well as ibuprofen. Medium chain triglyceride (MCT) oil was prescribed at 6 months of age, but the patient could not tolerate the product due to its taste and only started taking MCT at 3 years of age. 

The main symptoms holding the child back in life were recurrent muscle pain and fatigue, which resolved with fluids and rest. At a clinical review at 4 years of age, the child’s diet was shifted to include a greater proportion of lean protein. She continues to receive MCT supplementation. 

The clinical condition of the child continues to improve; she attends a full-time kindergarten and successfully spent a week at Disney parks. She is able to participate in extracurricular activities. She eats frequently and no longer complains of muscle pain. In the past year, she has not been admitted for intercurrent illness. 

Cost vs Benefit

In this single case study, we see clearly how the implementation of newborn screening allowed physicians to initiate investigations that led to a diagnosis of CPT 2 deficiency, which then allowed for early intervention. 

“As a consequence of the newborn screening, we suggest early treatment and timely intervention during illness likely prevented hypoglycemia and may have contributed to her normal neurological development and absence of cardiac involvement,” Mador-House and colleagues wrote. 

Although the patient had to go through multiple hospital admissions during her first few years of life, eventually her clinical condition stabilized, and she was able to lead a relatively normal life. This clearly demonstrates the clinical benefits of early diagnosis and treatment. 

The million-dollar question is whether a single case picked up via newborn screening out of a total of 220,000 newborns is sufficient evidence to make the case that CPT 2 deficiency should be offered as a newborn screening test at more healthcare centers. 

Read more about long chain fatty acid oxidation disorder epidemiology 

The difficulty of answering that question lies in the scarcity of data on this particular issue. Ironically, more data would require increased implementation of newborn screening for CPT 2 deficiency in more healthcare facilities. 

Tajima and colleagues have this to say: “In view of the fact that [newborn screening] for CPT 2 deficiency has yet to be adopted internationally, we hope that our initiative will contribute greatly to increasing interest in the methods suggested for detecting this potentially fatal disease.” 


Mador-House R, Liu Z, Dyack S. Detection of early onset carnitine palmitoyltransferase II deficiency by newborn screening: should CPT II deficiency be a primary disease target?Int J Neonatal Screen. Published online August 13, 2021. doi:10.3390/ijns7030055

Tajima G, Hara K, Yuasa M. Carnitine palmitoyltransferase II deficiency with a focus on newborn screeningJ Hum Genet. Published online December 4, 2018. doi:10.1038/s10038-018-0530-z