SLC22A5 gene
Also known as: Carnitine Transport Defect; Carnitine Uptake Defect; CDSP
OMIM#212140 https://omim.org/entry/212140
1. The disease:
Systemic primary carnitine deficiency (CDSP) is a disorder of the carnitine cycle that results in defective fatty acid oxidation.
2. The symptoms:
It encompasses a broad clinical spectrum as:
Infantile metabolic (hepatic) presentation: affected children can present between age three months and two years with episodes of metabolic decompensation triggered by fasting or common illnesses such as upper-respiratory tract infection or gastroenteritis. These episodes are characterized clinically by poor feeding, irritability, lethargy, and hepatomegaly. Laboratory evaluations usually reveal hypoketotic hypoglycemia (hypoglycemia with minimal or no ketones in urine), hyperammonemia, and elevated liver transaminases. If affected children are not treated with intravenous dextrose infusion during episodes of metabolic decompensation, they may develop coma and die.
Childhood myopathic (cardiac) presentation: It can manifest between age two and four years, indicating that the myopathic manifestations of CDSP may develop over a longer period of time. Myopathic manifestations include dilated cardiomyopathy, hypotonia, skeletal muscle weakness, and elevated serum creatine kinase (CK). Death from cardiac failure can occur before the diagnosis is established, indicating that this presentation can be fatal if not treated. Older children may also develop the infantile presentation.
Adulthood presentation: Several women have been diagnosed with CDSP after newborn screening identified low carnitine levels in their infants. About half of those women complained of fatigability, whereas the other half were asymptomatic. One woman was found to have dilated cardiomyopathy, and another had arrhythmias. During pregnancy, minor symptoms as well as cardiac arrhythmias can worsen. Asymptomatic adult males with have also been reported.
3. Actions to take in case of early diagnosis
- Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in the SLC22A5 gene) should continue breastfeeding and AVOID FASTING. Early treatment is crucial in preventing chronic symptoms.
- Biochemical correlation is essential for confirming diagnosis with very low plasma free and total carnitine concentrations. Biochemical NBS with tandem mass spectrometry can also help.
- CDSP is a lifelong disease that requires lifetime management and regular follow-up with a metabolic physician and a multidisciplinary approach to care.
- Strict avoidance of fasting along with carnitine therapy is the standard treatment.
- Oral levocarnitine (L-carnitine) supplementation of 100-400 mg/kg/day in three divided doses is usually required. Oral carnitine treatment is required for lifelong treatment of the disease. The prognosis is extremely good as long as oral carnitine supplementation is maintained.
- Genetic counseling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
Orphanet: https://www.orpha.net/consor/cgi-bin/Disease_Search_Simple.php?lng=FR
Biblio: El-Hattab AW. Systemic Primary Carnitine Deficiency. In: Adam MP, Everman DB, Mirzaa GM, et al., eds. GeneReviews(®). Seattle (WA): University of Washington, Seattle (https://www.ncbi.nlm.nih.gov/books/NBK84551/)