In the Journal of Infection and Chemotherapy, Ishige and colleagues reported the case study of a patient who was diagnosed with primary carnitine deficiency, a fatty acid oxidation disorder, after suffering a bout of other illnesses. 

The case study, as reported, details a 1-year-old female child who had a 5-day history of vomiting and diarrhea. She was previously administered cefcapene pivoxil hydrochloride hydrate (CFPN-PI) and intravenous glucose when she was seen at a clinic. Her symptoms subsided only temporarily, and she was admitted for hospitalization with a working diagnosis of acute gastroenteritis. 

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The patient was born at 37 weeks weighing 3210 g. Newborn screening results on day 5 were normal; however, acylcarnitine profiling was not carried out due to governmental policy. Her only medical history prior to her current hospitalization was infection of exanthem subitum. 

Her vaccination records revealed that she had not received a rotavirus vaccination. No 1 in her family has an inherited metabolic disease. 

Upon physical examination, her physicians noted a hard, enlarged, and palpable liver. Her laboratory results revealed elevated serum creatinine kinase (1033 mg/dL) and hypoglycemia (glucose levels of 57 mg/dL). A stool antigen test revealed the presence of the rotavirus antigen. 

“The patient was diagnosed with rotavirus gastroenteritis and liver dysfunction for which she received isotonic fluid infusions with glucose and liver-supporting therapy,” Ishige and colleagues wrote. 

Liver function tests revealed impaired liver protein synthesis. Abdominal computed tomography revealed a markedly enlarged liver with diffuse low absorbance. The child’s physicians added acute hepatitis into her list of diagnoses. 

Her physicians suspected fatty liver disease and started her on a low-fat diet with glucose infusion. Liver function test results improved on day 12, and she was discharged on day 14. 

“We suspected that a beta-oxidation deficiency or secondary carnitine deficiency, perhaps due to the CFPN-PI she had received at the clinic, accounted for the fat accumulation in the liver,” her physicians wrote. “In support, tandem mass spectrometry at the time of hospitalization showed that the free carnitine level in plasma was extremely low.” 

Three months later, additional tests revealed that free carnitine levels were low (1.50 mmol/L) and free carnitine clearance rate was high (46.7%). Her physicians diagnosed her with systemic primary carnitine deficiency. This diagnosis was confirmed by the reduced enzymatic activity of organic carnitine in the skin fibroblasts. Her physicians prescribed her oral levocarnitine (L-carnitine, 100 mg/kg per day), which caused her free carnitine levels to increase to 11.6 mmol/L. 

The Challenge of Diagnosing Primary Carnitine Deficiency 

In the case of the patient described, it is important to note that she first presented with vomiting and diarrhea — a relatively common set of symptoms seen among children. This is often due to food poisoning (though there are notable exceptions), which usually self-resolves with enough fluids and rest. 

However, this patient was found to have another peculiar sign when an abdominal examination was performed — a hard, enlarged, and palpable liver. This warranted further investigations. 

“Liver dysfunction due to rotavirus gastroenteritis has been reported; however, acute hepatitis due to this disease is very rare,” Ishige and colleagues wrote. 

The patient was diagnosed with rotavirus gastroenteritis and acute hepatitis, which was adequately treated by her physicians. 

It was only after further blood investigations were carried out that the patient was found to have low levels of free carnitine and that her free carnitine clearance rate was abnormally high, resulting in a diagnosis of systemic primary carnitine deficiency. 

Why was this disease not picked up earlier during her newborn screening test? This seems to be the result of an unfortunate series of events that were beyond the control of either hospital administrators or the physicians in charge of her care.

“Acylcarnitine profiling was not performed because she was born before the commencement of the expanded newborn tandem mass screening in Japan,” the study authors wrote. 

Read more about long chain fatty acid oxidation disorder epidemiology 

In other words, had the patient been born slightly later when newborn tandem mass screening had already been implemented nationwide in Japan, her diagnosis of primary carnitine deficiency would have been likely picked up within the first few days of life. 

In the Journal of Human Genetics, Tajima and colleagues wrote about how carnitine palmitoyltransferase 2 deficiency was first included as a newborn screening test in Japan as a pilot study between 2004 and 2012. It successfully detected the disease in approximately 1 out of every 248,627 patients detected. However, a child was recorded to have passed newborn screening but was later diagnosed with carnitine palmitoyltransferase 2 deficiency with acute hypoglycemic encephalopathy. 

Nevertheless, acylcarnitine profiling was included in newborn dried blood spots in Japan. So far, epidemiological studies reveal that the frequency of primary carnitine deficiency in Japan is 1:40,000, compared to 1:142,000 in the United States. The prognosis of patients diagnosed with primary carnitine deficiency from newborn screening is excellent with the commencement of treatment. 

It is important to note that many parents and carers suffer the same fate as those described in the case study due to inadequate/absent newborn screening programs. This could be due to a lack of funds or a lack of political willpower to initiate and maintain a program of which the yield is relatively little. However, newborn screening programs for this and other diseases should be implemented where possible simply because it offers something utterly priceless: giving children who are ill the best shot at a normal, healthy life. 


Ishige M, Fuchigami T, Furukawa M, et al. Primary carnitine deficiency with severe acute hepatitis following rotavirus gastroenteritisJ Infect Chemother. Published online June 10, 2019. doi:10.1016/j.jiac.2019.04.020

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

Longo N. Primary carnitine deficiency and newborn screening for disorders of the carnitine cycleAnn Nutr Metab. Published online December 9, 2016. doi:10.1159/000448321