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Carnitine palmitoyl transferase II deficiency, severe infantile form

MedGen UID:
322211
Concept ID:
C1833511
Disease or Syndrome
Synonyms: CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY WITH HYPOKETOTIC HYPOGLYCEMIA; CARNITINE PALMITOYLTRANSFERASE II DEFICIENCY, HEPATOCARDIOMUSCULAR; Carnitine palmitoyltransferase II deficiency, infantile; CPT II DEFICIENCY, HEPATIC; CPT II deficiency, infantile; CPT2 DEFICIENCY, INFANTILE
Modes of inheritance:
Autosomal recessive inheritance
MedGen UID:
141025
Concept ID:
C0441748
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele).
 
Gene (location): CPT2 (1p32.3)
 
Monarch Initiative: MONDO:0010914
OMIM®: 600649
Orphanet: ORPHA228305

Disease characteristics

Excerpted from the GeneReview: Carnitine Palmitoyltransferase II Deficiency
Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of long-chain fatty-acid oxidation. The three clinical presentations are lethal neonatal form, severe infantile hepatocardiomuscular form, and myopathic form (which is usually mild and can manifest from infancy to adulthood). While the former two are severe multisystemic diseases characterized by liver failure with hypoketotic hypoglycemia, cardiomyopathy, seizures, and early death, the latter is characterized by exercise-induced muscle pain and weakness, sometimes associated with myoglobinuria. The myopathic form of CPT II deficiency is the most common disorder of lipid metabolism affecting skeletal muscle and the most frequent cause of hereditary myoglobinuria. Males are more likely to be affected than females. [from GeneReviews]
Authors:
Thomas Wieser   view full author information

Additional descriptions

From OMIM
Carnitine palmitoyltransferase II deficiency is an inherited disorder of mitochondrial long-chain fatty acid oxidation. The infantile form usually presents between 6 and 24 months of age with recurrent attacks of hypoketotic hypoglycemia causing loss of consciousness and seizures, liver failure, and transient hepatomegaly. Some children also have heart involvement with cardiomyopathy and arrhythmia. Episodes are triggered by infections, fever, or fasting. Laboratory studies usually indicate hyperammonemia, metabolic acidosis, and hypoketotic hypoglycemia with elevated levels of creatine kinase (summary by Longo et al., 2006). See also the lethal neonatal (608836) and adult-onset (255110) forms of the disorder, which are also caused by mutation in the CPT2 gene.  http://www.omim.org/entry/600649
From MedlinePlus Genetics
Carnitine palmitoyltransferase II (CPT II) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). There are three main types of CPT II deficiency: a lethal neonatal form, a severe infantile hepatocardiomuscular form, and a myopathic form.

The severe infantile hepatocardiomuscular form of CPT II deficiency affects the liver, heart, and muscles. Signs and symptoms usually appear within the first year of life. This form involves recurring episodes of hypoketotic hypoglycemia, seizures, an enlarged liver (hepatomegaly), cardiomyopathy, and arrhythmia. Problems related to this form of CPT II deficiency can be triggered by periods of fasting or by illnesses such as viral infections. Individuals with the severe infantile hepatocardiomuscular form of CPT II deficiency are at risk for liver failure, nervous system damage, coma, and sudden death.

The myopathic form is the least severe type of CPT II deficiency. This form is characterized by recurrent episodes of muscle pain (myalgia) and weakness and is associated with the breakdown of muscle tissue (rhabdomyolysis). The destruction of muscle tissue releases a protein called myoglobin, which is processed by the kidneys and released in the urine (myoglobinuria). Myoglobin causes the urine to be red or brown. This protein can also damage the kidneys, in some cases leading to life-threatening kidney failure. Episodes of myalgia and rhabdomyolysis may be triggered by exercise, stress, exposure to extreme temperatures, infections, or fasting. The first episode usually occurs during childhood or adolescence. Most people with the myopathic form of CPT II deficiency have no signs or symptoms of the disorder between episodes.

The lethal neonatal form of CPT II deficiency becomes apparent soon after birth. Infants with this form of the disorder develop respiratory failure, seizures, liver failure, a weakened heart muscle (cardiomyopathy), and an irregular heart beat (arrhythmia). Affected individuals also have low blood glucose (hypoglycemia) and a low level of ketones, which are produced during the breakdown of fats and used for energy. Together these signs are called hypoketotic hypoglycemia. In many cases, the brain and kidneys are also structurally abnormal. Infants with the lethal neonatal form of CPT II deficiency usually live for a few days to a few months.  https://medlineplus.gov/genetics/condition/carnitine-palmitoyltransferase-ii-deficiency

Clinical features

From HPO
Primary dilated cardiomyopathy
MedGen UID:
2880
Concept ID:
C0007193
Disease or Syndrome
Familial dilated cardiomyopathy is a genetic form of heart disease. It occurs when heart (cardiac) muscle becomes thin and weakened in at least one chamber of the heart, causing the open area of the chamber to become enlarged (dilated). As a result, the heart is unable to pump blood as efficiently as usual. To compensate, the heart attempts to increase the amount of blood being pumped through the heart, leading to further thinning and weakening of the cardiac muscle. Over time, this condition results in heart failure.\n\nIt usually takes many years for symptoms of familial dilated cardiomyopathy to cause health problems. They typically begin in mid-adulthood, but can occur at any time from infancy to late adulthood. Signs and symptoms of familial dilated cardiomyopathy can include an irregular heartbeat (arrhythmia), shortness of breath (dyspnea), extreme tiredness (fatigue), fainting episodes (syncope), and swelling of the legs and feet. In some cases, the first sign of the disorder is sudden cardiac death. The severity of the condition varies among affected individuals, even in members of the same family.
Cardiomegaly
MedGen UID:
5459
Concept ID:
C0018800
Finding
Increased size of the heart, clinically defined as an increased transverse diameter of the cardiac silhouette that is greater than or equal to 50% of the transverse diameter of the chest (increased cardiothoracic ratio) on a posterior-anterior projection of a chest radiograph or a computed tomography.
Ventricular tachycardia
MedGen UID:
12068
Concept ID:
C0042514
Finding
A tachycardia originating in the ventricles characterized by rapid heart rate (over 100 beats per minute) and broad QRS complexes (over 120 ms).
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Vomiting
MedGen UID:
12124
Concept ID:
C0042963
Sign or Symptom
Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.
Macrovesicular hepatic steatosis
MedGen UID:
373290
Concept ID:
C1837256
Finding
A form of hepatic steatosis characterized by the presence of large, lipid-laden vesicles in the affected hepatocytes.
Lethargy
MedGen UID:
7310
Concept ID:
C0023380
Sign or Symptom
A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks.
Seizure
MedGen UID:
20693
Concept ID:
C0036572
Sign or Symptom
A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.
Respiratory arrest
MedGen UID:
57878
Concept ID:
C0162297
Pathologic Function
Cessation of breathing function.
Elevated circulating hepatic transaminase concentration
MedGen UID:
116013
Concept ID:
C0235996
Finding
Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage.
Elevated circulating creatine kinase concentration
MedGen UID:
69128
Concept ID:
C0241005
Finding
An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.
Hypoketotic hypoglycemia
MedGen UID:
344733
Concept ID:
C1856438
Finding
A decreased concentration of glucose in the blood associated with a reduced concentration of ketone bodies.
Increased circulating lactate dehydrogenase concentration
MedGen UID:
1377250
Concept ID:
C4477095
Finding
An elevated level of the enzyme lactate dehydrogenase in the blood circulation.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.

Term Hierarchy

Follow this link to review classifications for Carnitine palmitoyl transferase II deficiency, severe infantile form in Orphanet.

Recent clinical studies

Etiology

Serra G, Antona V, Insinga V, Morgante G, Vassallo A, Placa S, Piro E, Salerno S, Schierz IAM, Gitto E, Giuffrè M, Corsello G
Ital J Pediatr 2024 Apr 14;50(1):67. doi: 10.1186/s13052-024-01632-x. PMID: 38616285Free PMC Article
Yazıcı H, Ak G, Çelik MY, Erdem F, Yanbolu AY, Er E, Bozacı AE, Güvenç MS, Aykut A, Durmaz A, Canda E, Uçar SK, Çoker M
J Pediatr Endocrinol Metab 2024 Jan 29;37(1):33-41. Epub 2023 Nov 7 doi: 10.1515/jpem-2023-0298. PMID: 37925743
Blah N, Sudrié-Arnaud B, Torre S, Marret S, Bekri S, Tebani A
Int J Mol Sci 2018 Sep 27;19(10) doi: 10.3390/ijms19102950. PMID: 30262761Free PMC Article

Diagnosis

Yazıcı H, Ak G, Çelik MY, Erdem F, Yanbolu AY, Er E, Bozacı AE, Güvenç MS, Aykut A, Durmaz A, Canda E, Uçar SK, Çoker M
J Pediatr Endocrinol Metab 2024 Jan 29;37(1):33-41. Epub 2023 Nov 7 doi: 10.1515/jpem-2023-0298. PMID: 37925743
Çakar NE, Gör Z, Yeşil G
Ideggyogy Sz 2021 Mar 30;74(3-4):135-138. doi: 10.18071/isz.74.0135. PMID: 33938664
Joshi PR, Zierz S
Molecules 2020 Apr 13;25(8) doi: 10.3390/molecules25081784. PMID: 32295037Free PMC Article
Tajima G, Hara K, Yuasa M
J Hum Genet 2019 Feb;64(2):87-98. Epub 2018 Dec 4 doi: 10.1038/s10038-018-0530-z. PMID: 30514913
Blah N, Sudrié-Arnaud B, Torre S, Marret S, Bekri S, Tebani A
Int J Mol Sci 2018 Sep 27;19(10) doi: 10.3390/ijms19102950. PMID: 30262761Free PMC Article

Prognosis

Serra G, Antona V, Insinga V, Morgante G, Vassallo A, Placa S, Piro E, Salerno S, Schierz IAM, Gitto E, Giuffrè M, Corsello G
Ital J Pediatr 2024 Apr 14;50(1):67. doi: 10.1186/s13052-024-01632-x. PMID: 38616285Free PMC Article
Tan YY, Fong WYN, Chan CJ, Chandran S
BMJ Case Rep 2022 Dec 19;15(12) doi: 10.1136/bcr-2022-251321. PMID: 36535739Free PMC Article
Çakar NE, Gör Z, Yeşil G
Ideggyogy Sz 2021 Mar 30;74(3-4):135-138. doi: 10.18071/isz.74.0135. PMID: 33938664
Tajima G, Hara K, Yuasa M
J Hum Genet 2019 Feb;64(2):87-98. Epub 2018 Dec 4 doi: 10.1038/s10038-018-0530-z. PMID: 30514913
Melek E, Bulut FD, Atmış B, Yılmaz BŞ, Bayazıt AK, Mungan NÖ
J Pediatr Endocrinol Metab 2017 Feb 1;30(2):237-239. doi: 10.1515/jpem-2016-0324. PMID: 28085674

Clinical prediction guides

Serra G, Antona V, Insinga V, Morgante G, Vassallo A, Placa S, Piro E, Salerno S, Schierz IAM, Gitto E, Giuffrè M, Corsello G
Ital J Pediatr 2024 Apr 14;50(1):67. doi: 10.1186/s13052-024-01632-x. PMID: 38616285Free PMC Article

Supplemental Content

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    Clinical resources

    Practice guidelines

    • PubMed
      See practice and clinical guidelines in PubMed. The search results may include broader topics and may not capture all published guidelines. See the FAQ for details.

    Curated

    • ACMG ACT, 2022
      American College of Medical Genetics and Genomics, Newborn Screening ACT Sheet, Increased C16 and/or C18:1 Acylcarnitine, Carnitine Palmitoyltransferase II (CPT II) Deficiency and Carnitine Acylcarnitine Translocase (CACT) Deficiency, 2022
    • ACMG Algorithm, 2022
      American College of Medical Genetics and Genomics, Algorithm, C16 +/- C18:1 Elevated: CPT II or CACT, 2022

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