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Carnitine palmitoyl transferase II deficiency, severe infantile form
Disease definition
The severe infantile form of carnitine palmitoyltransferase II (CPT II) deficiency (see this term), an inherited disorder that affects mitochondrial oxidation of long chain fatty acids (LCFA), is the early-onset form of the disease.
ORPHA:228305
Classification level: Subtype of disorder- Synonym(s):
- CPT2, hepatocardiomuscular form
- CPT2, severe infantile form
- CPTII, hepatocardiomuscular form
- CPTII, severe infantile form
- Carnitine palmitoyl transferase II deficiency, hepatocardiomuscular form
- Carnitine palmitoyl transferase deficiency type 2, hepatocardiomuscular form
- Carnitine palmitoyl transferase deficiency type 2, severe infantile form
- Prevalence: <1 / 1 000 000
- Inheritance: Autosomal recessive
- Age of onset: Infancy, Neonatal
- ICD-10: E71.3
- ICD-11: 5C52.00
- OMIM: 600649
- UMLS: C1833511
- MeSH: -
- GARD: -
- MedDRA: -
Summary
Epidemiology
It has been identified in approximately 30 families.
Clinical description
Presentation can be in the newborn period but most cases have an age of onset between 6 and 24 months. The disease is characterized by a severe fasting intolerance leading to metabolic derangements of hypoketotic hypoglycemia, resulting in coma and seizures, and hepatic encephalopathy leading to liver failure. There is associated skeletal muscle myopathy and cardiomyopathy which can lead to fatal paroxysmal cardiac arrhythmias.
Etiology
Missense mutations in the CPT2 gene result in the infantile form of CPT II deficiency. Contrary to the adult myopathic form (see this term), no S113L mutations have ever been detected in the infantile form.
Diagnostic methods
The diagnosis is made by an initial tandem mass spectrometric analysis of serum/plasma acylcarnitines followed by mutation analysis and measurements of CPT2 enzyme activity in fresh circulating lymphocytes, muscle or skin fibroblasts.
Differential diagnosis
The differential diagnosis should include carnitine-acylcarnitine translocase deficiency (CACT) and very-long-chain acyl-CoA dehydrogenase deficiency (see these terms).
Antenatal diagnosis
Prenatal diagnosis is available using both molecular and enzymatic analysis.
Genetic counseling
Transmission is autosomal recessive.
Management and treatment
Treatment is based on prevention of the fasting intolerance by providing carbohydrate calories during periods of febrile or gastrointestinal illness. When well, a low-fat and high-carbohydrate diet is initiated and for the most severe forms of the disease overnight feeding with a slow release carbohydrate such as corn starch can be implemented. Anaplerotic therapy with triheptanoin has also been suggested as a therapy. Plasma carnitine levels may be low in the disease and L-carnitine administration is also used in the treatment but this approach has not been validated in a controlled study.
Prognosis
The severe infantile form may lead to sudden death during infancy due, in general, to paroxysmal cardiac arrhythmias. This is particularly true for undiagnosed cases. Early diagnosis through newborn screening has identified cases pre-symptomatically and outcomes appear to be improving as a result.
A summary on this disease is available in Deutsch (2010) Español (2010) Français (2010) Italiano (2010) Nederlands (2010)
Detailed information
General public
- Article for general public
- Svenska (2018) - Socialstyrelsen
Guidelines
- Emergency guidelines
- English (2012, pdf) - Brit Inher Metab Dis Group
- Clinical practice guidelines
- Français (2021) - PNDS
Disease review articles
- Clinical genetics review
- English (2019) - GeneReviews
: produced/endorsed by ERN(s)
: produced/endorsed by FSMR(s)
Additional information