Abstract
Systemic primary carnitine deficiency (PCD) is a genetic disorder caused by decreased or absent organic cation transporter type 2 (OCTN2) carnitine transporter activity, resulting in low serum carnitine levels and decreased carnitine accumulation inside cells. In early life, PCD is usually diagnosed as a metabolic decompensation, presenting as hypoketotic hypoglycemia, Reye syndrome, or sudden infant death; in childhood, PCD presents with skeletal or cardiac myopathy. However, the clinical presentation of PCD characterized by autism spectrum disorder (ASD) with intellectual disability (ID) has seldom been reported in the literature. In this report, we describe the clinical features of a seven-year-old girl diagnosed with PCD who presented atypical features of the disease, including a developmental delay involving language skills, concentration, and attention span, as well as autistic features and brain alterations apparent in magnetic resonance imaging. We aim to highlight the difficulties related to the diagnostic and therapeutic approaches used to diagnose such patients. The case reported here presented typical signs of PCD, including frequent episodes of hypoglycemia, generalized muscle weakness, decreased muscle mass, and physical growth deficits. A molecular genetic study confirmed the definitive diagnosis of the disease (c.1345T>G (p.Y449D)) in gene SLC22A5, located in exon 8. PCD can be accompanied by less common clinical signs, which may delay its diagnosis because the resulting global clinical picture can closely resemble other metabolic disorders. In this case, the patient was prescribed a carnitine-enriched diet, as well as oral carnitine at a dose of 100 mg/kg/day. PCD has a better prognosis if it is diagnosed and treated early; however, a high level of clinical suspicion is required for its timely and accurate diagnosis.
Highlights
Systemic primary carnitine deficiency (PCD; Online Mendelian Inheritance in Man (OMIM): 212140) is an autosomal recessive disorder, associated with decreased carnitine uptake across plasma membranes because of a deficiency in organic cation transporter type 2 (OCTN2), encoded by the SLC22A5 gene on chromosome 5q31 [1,2]
Primary carnitine deficiency classically presents as a hypoketotic, hypoglycemic encephalopathy, which is often associated with hepatomegaly, elevated transaminase levels, hyperammonemia, cardiomyopathy, pericardial effusion, muscle weakness, altered gastrointestinal motility, and recurrent attacks of abdominal pain and diarrhea, along with anemia and repeated infections during early life [8,9,10,11]
We presented a clinical case of childhood-onset PCD with both rare clinical characteristics and common ones
Summary
Systemic primary carnitine deficiency (PCD; Online Mendelian Inheritance in Man (OMIM): 212140) is an autosomal recessive disorder, associated with decreased carnitine uptake across plasma membranes because of a deficiency in organic cation transporter type 2 (OCTN2), encoded by the SLC22A5 gene on chromosome 5q31 [1,2]. Secondary carnitine deficiency occurs in other metabolic disorders, including organic acidemia and fatty acid oxidation defects, such as very-long-chain acyl-CoA dehydrogenase, medium-chain acyl-CoA dehydrogenase, long-chain hydroxyacyl-CoA dehydrogenase, or carnitine palmitoyltransferase II deficiencies. Drugs such as cyclosporine and valproate can cause carnitine deficiency, renal tubular dysfunction, and malnutrition, and complete parenteral nutrition may result in secondary carnitine deficiency [11]. We report the interesting and novel case of a female child in which we identified a PCD gene mutation This patient presented atypical signs for PCD, such as ASD and ID, as well as brain magnetic resonance imaging (MRI) alterations. We hope the description of this phenotype–genotype will help guide clinicians in their differential diagnosis of children presenting ASD and developmental growth delay
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