Clinical varieties of carnitine and carnitine palmitoyltransferase deficiency

doi:10.1016/S0009-9120(87)80090-5

Clinical Biochemistry

Volume 20, Issue 1, February 1987, Pages 1-7

https://doi.org/10.1016/S0009-9120(87)80090-5 Get rights and content

Several clinical entities are associated with disorders of fatty acid oxidation or transfer across the inner mitochondrial membrane. Over 40 cases of the primary carnitine deficiency syndrome have been reported to date and various subtypes have been characterized. This represents a large clinical spectrum.

The deficiency of carnitine in muscle is at the basis of a syndrome characterized by muscle weakness and lipid storage myopathy. The systemic form of carnitine deficiency is more generalized and includes recurrent episodes of hepatic encephalopathy as well as lipid storage in muscle, liver and heart. In one subtype, hypoglycemia upon fasting and cardiomyopathy are found. There are also several causes of secondary carnitine deficiency states which are either acquired or associated with inborn errors of metabolism (organic acidurias, defects of acyl-CoA dehydrogenases).

Clinically, Carnitine palmitoyltransferase (CPT) deficiency is a rather homogeneous syndrome presenting with recurrent episodes of myoglobinuria provoked by fasting or prolonged exercise. The only exception is an infantile variety associated with severe hypoglycemia and hepatic CPT deficiency. Using malonyl-CoA, a specific inhibitor of CPT-I, we had suggestions in five adult patients with myoglobinuria that CPT-II is lacking in muscle, liver and platelets while CPT-I is above the control level. The enzyme abnormality seems partial and limited to CPT-II or to its binding to the inner mitochondrial membrane.

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Page et al. (Page et al., 2021) suggested employing an algorithm that incorporated all of the procedures required in determining the study's relevant content, as shown in the flow chart in Figure 1. Two separate carnitine deficiency conditions have been recorded, albeit establishing a precise difference between “primary” and “secondary” carnitine deficit can be problematic in certain circumstances (Angelini et al., 1987). Primary carnitine deficiency (PCD) is an autosomal recessive disorder characterized by a lack of plasma membrane carnitine transport owing to a shortcoming in the OCTN2 carnitine transporter.
Carnitine is a medically needful nutrient that contributes in the production of energy and the metabolism of fatty acids. Bioavailability is higher in vegetarians than in people who eat meat. Deficits in carnitine transporters occur as a result of genetic mutations or in combination with other illnesses such like hepatic or renal disease. Carnitine deficit can arise in diseases such endocrine maladies, cardiomyopathy, diabetes, malnutrition, aging, sepsis, and cirrhosis due to abnormalities in carnitine regulation. The exogenously provided molecule is obviously useful in people with primary carnitine deficits, which can be life-threatening, and also some secondary deficiencies, including such organic acidurias: by eradicating hypotonia, muscle weakness, motor skills, and wasting are all improved l-carnitine (LC) have reported to improve myocardial functionality and metabolism in ischemic heart disease patients, as well as athletic performance in individuals with angina pectoris. Furthermore, although some intriguing data indicates that LC could be useful in a variety of conditions, including carnitine deficiency caused by long-term total parenteral supplementation or chronic hemodialysis, hyperlipidemias, and the prevention of anthracyclines and valproate-induced toxicity, such findings must be viewed with caution.
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Frailty is a geriatric syndrome characterized by muscle weakness, sarcopenia, and fatigue, and is associated with several adverse health outcomes, including disability. Design of therapeutic interventions for geriatric frailty has been challenging and may be because of inadequate understanding of its biological underpinnings. Carnitine is important for energy production in skeletal muscles and there seems to be a negative correlation between advancing age and muscle carnitine levels. Carnitine deficiency may therefore contribute to geriatric frailty. Age-associated carnitine deficiency from a variety of etiologies, including organic cation transporter (OCTN2) mutation and carnitine palmitoyltransferase II (CPT) deficiency, may potentially explain the relationship between carnitine-associated mitochondrial dysfunction and geriatric frailty. Development of therapeutic agents capable of prevention or reversal of carnitine deficiency in older adults may minimize the occurrence of frailty in geriatric populations.
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A 48-year-old male patient had two episodes of fever, headache, confusion and seizures following an upper respiratory tract infection. Electroencephalography (EEG) revealed diffuse slowing of background activity. Plasma free carnitine and serum lipid levels were low; fecal fat content and serum antigliadin antibodies were elevated. Duodenal biopsy was compatible with gluten enteropathy. Symptoms improved after the patient was started on a gluten-free diet and carnitine replacement therapy. No recurrence was observed within a four-year follow-up. Carnitine deficiency in adulthood is unusual, and encephalopathy due to carnitine deficiency as a result of celiac disease has not been described previously.

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Invited reviewClinical varieties of carnitine and carnitine palmitoyltransferase deficiency

Lancet

J Neurol Sci

J Neurol Sci

J Pediatr

J Pediatr

J Pediatr

J Neurol Sci

Lancet

Lancet

Lancet

Am J Obstet Gynecol

Clin Chim Acta

J Pediatr

Carnitine deficiency of human skeletal muscle with associated lipid storage myopathy: a new syndrome

Science

Muscle carnitine deficiency

Arch Neurol

Weakness associated with the pathological presence of lipid in skeletal muscle: a detailed study of a patient with carnitine deficiency

J Neurol Neurosurg Psychiatry

Carnitine deficiency of skeletal muscle: report of a treated case

Neurology

A case of lipid storage myopathy with carnitine deficiency

Eur Neurol

Hereditary carnitine deficiency of muscle

Neurology

Carnitine deficiency: acute postpartum crisis

Ann Neurol

Muscle carnitine deficiency and fatal cardiomyopathy

Neurology

Carnitine “deficiency”: lack of response to carnitine therapy

Neurology

Nearly fatal muscle carnitine deficiency with full recovery after replacement therapy

Neurology

Muscle carnitine deficiency: fatty acid metabolism in cultured fibroblasts and muscle cells

Neurology

Metabolic abnormalities in a patient with muscular carnitine deficiency

J Inherited Metab Dis

Invited review
Clinical varieties of carnitine and carnitine palmitoyltransferase deficiency