Primary carnitine deficiency in two sisters with intractable epilepsy and reversible metabolic cardiomyopathy: Two case reports

Abstract

Primary carnitine deficiency (PCD) is a disorder of the carnitine cycle that results in defective fatty acid oxidation. When carnitine cannot be transported into the cells, fatty acid oxidation is impaired, resulting a variety of symptoms, such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction. The clinical manifestations and outcomes of different cases with PCD vary among patients. The present case report focused on two sisters with PCD. The younger sister presented with intractable epilepsy, and the older sister presented with reversible metabolic cardiomyopathy. Potential mutations in the SLC22A5 gene were investigated within the family, and a nonsense mutation [c.760C>T (p.R254X)] was identified in four family members. The two sisters harbored homozygous mutations, whereas their parents presented heterozygous mutations. Metabolic disease screening revealed low plasma free carnitine levels (<5 µmol/l) in the two sisters. The plasma free carnitine levels of their parents were normal, and they were asymptomatic. PCD in the two patients was managed using oral levocarnitine. The metabolic cardiomyopathy of the older sister improved following 3 months of treatment. However, the epilepsy of the younger sister was recurrent with oral antiepileptic therapy lasting one year and eight months, and epilepsy was finally controlled following right cerebral resection. The present case report demonstrated that the clinical manifestations presented by patients with PCD within the same family were different. The results indicated that treatment with levocarnitine supplementation should be initiated as soon as possible before irreversible organ damage occurs. In addition, metabolic decompensation and cardiac muscle functions were improved following carnitine supplementation. The resection of the severely diseased unilateral brain combined with carnitine supplementation and antiepileptic therapy may be an effective treatment for PCD with intractable epilepsy complications.

Keywords: PCD; cardiomyopathy; encephalopathy; gene mutation.

Figure 1

Electroencephalogram of the patient with primary carnitine deficiency and intractable epilepsy recorded in November 2015. The electroencephalogram indicated large and slow waves originating from multiple right occipital areas and large paroxysmal wave rhythms in the left occipital area, indicated by arrows.

Figure 2

Brain MRI scans of the patient with primary carnitine deficiency and intractable epilepsy in November 2015. The brain MRI indicated a low signal in the right cerebral hemisphere on the T1-weighted image (right) and a high signal on the T2-weighted image (left), indicated by arrows.

Figure 3

Brain MRI scans of the patient with primary carnitine deficiency and intractable epilepsy in February 2016. The brain MRI indicated atrophy in the right cerebral hemisphere and an enlarged cortical lamellar necrosis, low signal in the right cerebral hemisphere on the T1-weighted image (right) and high signal on the T2-weighted image (left), indicated by arrows.

Figure 4

Brain MRI scans of the patient with primary carnitine deficiency and intractable epilepsy in August 2017. The brain MRI indicated a compensatory hydrocephalus in the right frontotemporal occipital lobe on the two different levels on the T2-weighted image (left and right image), indicated by arrows.

Figure 5

Nonsense homozygous mutation [c.760C>T (p.R254X)] in the SLC22A5 gene in the proband and her elder sister and heterozygous mutation in their parents. The arrows indicate the site of the mutation. (A), the proband; (B), the elder sister; (C), their mother; (D), their father.