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Carnitine palmitoyl transferase 1A deficiency

MedGen UID:
316820
Concept ID:
C1829703
Disease or Syndrome
Synonyms: Carnitine palmitoyl transferase 1 deficiency; Carnitine palmitoyltransferase 1A deficiency; Carnitine Palmitoyltransferase IA Deficiency; Carnitine palmitoyltransferase type I deficiency; CPT DEFICIENCY, HEPATIC, TYPE I; CPT deficiency, hepatic, type IA; CPT I DEFICIENCY; CPT1A deficiency; Hepatic carnitine palmitoyltransferase 1 deficiency; Hepatic CPT1; L-CPT 1 deficiency
SNOMED CT: Carnitine palmitoyltransferase deficiency type 1 (238001003); Carnitine palmitoyltransferase I deficiency (238001003); Liver form of carnitine palmitoyltransferase deficiency (238001003); CPTI - Carnitine palmitoyltransferase deficiency type I (238001003); CPT1 - Carnitine palmitoyltransferase I deficiency (238001003)
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): CPT1A (11q13.3)
 
Monarch Initiative: MONDO:0009705
OMIM®: 255120
Orphanet: ORPHA156

Disease characteristics

Excerpted from the GeneReview: Carnitine Palmitoyltransferase 1A Deficiency
Carnitine palmitoyltransferase 1A (CPT1A) deficiency is a disorder of long-chain fatty acid oxidation. Clinical manifestations usually occur in an individual with a concurrent febrile or gastrointestinal illness when energy demands are increased; onset of symptoms is usually rapid. The recognized phenotypes are: acute fatty liver of pregnancy, in which the fetus has biallelic pathogenic variants in CPT1A that causes CPT1A deficiency; and hepatic encephalopathy, in which individuals (typically children) present with hypoketotic hypoglycemia and sudden onset of liver failure. Individuals with hepatic encephalopathy typically present with hypoglycemia, absent or low levels of ketones, and elevated serum concentrations of liver transaminases, ammonia, and total carnitine. Between episodes of hepatic encephalopathy, individuals appear developmentally and cognitively normal unless previous metabolic decompensation has resulted in neurologic damage. [from GeneReviews]
Authors:
Michael J Bennett  |  Avni B Santani   view full author information

Additional descriptions

From OMIM
Carnitine palmitoyltransfease I deficiency is an autosomal recessive metabolic disorder of long-chain fatty acid oxidation characterized by severe episodes of hypoketotic hypoglycemia usually occurring after fasting or illness. Onset is in infancy or early childhood (Bougneres et al., 1981)  http://www.omim.org/entry/255120
From MedlinePlus Genetics
Carnitine palmitoyltransferase I (CPT I) deficiency is a condition that prevents the body from using certain fats for energy, particularly during periods without food (fasting). The severity of this condition varies among affected individuals.

Signs and symptoms of CPT I deficiency often appear during early childhood. Affected individuals usually 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. People with CPT I deficiency can also have an enlarged liver (hepatomegaly), liver malfunction, and elevated levels of carnitine in the blood. Carnitine, a natural substance acquired mostly through the diet, is used by cells to process fats and produce energy. Individuals with CPT I deficiency are at risk for nervous system damage, liver failure, seizures, coma, and sudden death.

Problems related to CPT I deficiency can be triggered by periods of fasting or by illnesses such as viral infections. This disorder is sometimes mistaken for Reye syndrome, a severe disorder that may develop in children while they appear to be recovering from viral infections such as chicken pox or flu. Most cases of Reye syndrome are associated with the use of aspirin during these viral infections.  https://medlineplus.gov/genetics/condition/carnitine-palmitoyltransferase-i-deficiency

Clinical features

From HPO
Ketonuria
MedGen UID:
56402
Concept ID:
C0162275
Finding
High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state.
Dicarboxylic aciduria
MedGen UID:
343550
Concept ID:
C1856432
Finding
An increased concentration of dicarboxylic acid in the urine.
Cardiac arrhythmia
MedGen UID:
2039
Concept ID:
C0003811
Finding
Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both.
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.
Diarrhea
MedGen UID:
8360
Concept ID:
C0011991
Sign or Symptom
Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day.
Hepatomegaly
MedGen UID:
42428
Concept ID:
C0019209
Finding
Abnormally increased size of the liver.
Feeding difficulties
MedGen UID:
65429
Concept ID:
C0232466
Finding
Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.
Hepatic steatosis
MedGen UID:
398225
Concept ID:
C2711227
Disease or Syndrome
Steatosis is a term used to denote lipid accumulation within hepatocytes.
Coma
MedGen UID:
1054
Concept ID:
C0009421
Disease or Syndrome
The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.
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.
Hyporeflexia
MedGen UID:
195967
Concept ID:
C0700078
Finding
Reduction of neurologic reflexes such as the knee-jerk reaction.
Recurrent encephalopathy
MedGen UID:
376865
Concept ID:
C1850719
Finding
Recurrent episodes of brain dysfunction that may be triggered by factors such as metabolic disturbances or infections.
Motor delay
MedGen UID:
381392
Concept ID:
C1854301
Finding
A type of Developmental delay characterized by a delay in acquiring motor skills.
Hypotonia
MedGen UID:
10133
Concept ID:
C0026827
Finding
Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.
Muscle weakness
MedGen UID:
57735
Concept ID:
C0151786
Finding
Reduced strength of muscles.
Generalized hypotonia
MedGen UID:
346841
Concept ID:
C1858120
Finding
Generalized muscular hypotonia (abnormally low muscle tone).
Renal tubular acidosis
MedGen UID:
90
Concept ID:
C0001126
Disease or Syndrome
Acidosis owing to malfunction of the kidney tubules with accumulation of metabolic acids and hyperchloremia, potentially leading to complications including hypokalemia, hypercalcinuria, nephrolithiasis and nephrocalcinosis.
Elevated circulating aspartate aminotransferase concentration
MedGen UID:
57497
Concept ID:
C0151904
Finding
The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.
Elevated circulating alanine aminotransferase concentration
MedGen UID:
57740
Concept ID:
C0151905
Finding
An abnormally high concentration in the circulation of alanine aminotransferase (ALT).
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.
Transient hyperlipidemia
MedGen UID:
340608
Concept ID:
C1850722
Finding
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.
Hyperammonemia
MedGen UID:
1802066
Concept ID:
C5574662
Laboratory or Test Result
An increased concentration of ammonia in the blood.

Professional guidelines

PubMed

Janeiro P, Jotta R, Ramos R, Florindo C, Ventura FV, Vilarinho L, Tavares de Almeida I, Gaspar A
Eur J Pediatr 2019 Mar;178(3):387-394. Epub 2019 Jan 7 doi: 10.1007/s00431-018-03315-2. PMID: 30617651

Recent clinical studies

Etiology

Janeiro P, Jotta R, Ramos R, Florindo C, Ventura FV, Vilarinho L, Tavares de Almeida I, Gaspar A
Eur J Pediatr 2019 Mar;178(3):387-394. Epub 2019 Jan 7 doi: 10.1007/s00431-018-03315-2. PMID: 30617651
Sood V, Rawat D, Khanna R, Sharma S, Gupta PK, Alam S, Sarin SK
J Pediatr Gastroenterol Nutr 2017 Jun;64(6):869-875. doi: 10.1097/MPG.0000000000001510. PMID: 28045774
Dykema DM
Adv Neonatal Care 2012 Feb;12(1):23-7. doi: 10.1097/ANC.0b013e318242df6d. PMID: 22301540

Diagnosis

Janeiro P, Jotta R, Ramos R, Florindo C, Ventura FV, Vilarinho L, Tavares de Almeida I, Gaspar A
Eur J Pediatr 2019 Mar;178(3):387-394. Epub 2019 Jan 7 doi: 10.1007/s00431-018-03315-2. PMID: 30617651
Sood V, Rawat D, Khanna R, Sharma S, Gupta PK, Alam S, Sarin SK
J Pediatr Gastroenterol Nutr 2017 Jun;64(6):869-875. doi: 10.1097/MPG.0000000000001510. PMID: 28045774
de Sain-van der Velden MG, Diekman EF, Jans JJ, van der Ham M, Prinsen BH, Visser G, Verhoeven-Duif NM
Mol Genet Metab 2013 Sep-Oct;110(1-2):116-21. Epub 2013 Apr 13 doi: 10.1016/j.ymgme.2013.04.008. PMID: 23639448
Purevsuren J, Kobayashi H, Hasegawa Y, Yamada K, Takahashi T, Takayanagi M, Fukao T, Fukuda S, Yamaguchi S
Anal Bioanal Chem 2013 Feb;405(4):1345-51. Epub 2012 Nov 10 doi: 10.1007/s00216-012-6532-3. PMID: 23143007
Dykema DM
Adv Neonatal Care 2012 Feb;12(1):23-7. doi: 10.1097/ANC.0b013e318242df6d. PMID: 22301540

Therapy

Smart CL, Bratkovic D, Muller KR
Liver Transpl 2024 Jan 1;30(1):107-109. Epub 2023 Jul 12 doi: 10.1097/LVT.0000000000000207. PMID: 37432890
Lee BH, Kim YM, Kim JH, Kim GH, Kim JM, Kim JH, Woo KH, Yang SH, Kim CJ, Choi IH, Yoo HW
J Pediatr Gastroenterol Nutr 2015 Mar;60(3):e19-22. doi: 10.1097/MPG.0b013e3182a95a42. PMID: 23969540
Gillingham MB, Hirschfeld M, Lowe S, Matern D, Shoemaker J, Lambert WE, Koeller DM
Mol Genet Metab 2011 Nov;104(3):261-4. Epub 2011 Jun 28 doi: 10.1016/j.ymgme.2011.06.017. PMID: 21763168Free PMC Article

Prognosis

Janeiro P, Jotta R, Ramos R, Florindo C, Ventura FV, Vilarinho L, Tavares de Almeida I, Gaspar A
Eur J Pediatr 2019 Mar;178(3):387-394. Epub 2019 Jan 7 doi: 10.1007/s00431-018-03315-2. PMID: 30617651
Sood V, Rawat D, Khanna R, Sharma S, Gupta PK, Alam S, Sarin SK
J Pediatr Gastroenterol Nutr 2017 Jun;64(6):869-875. doi: 10.1097/MPG.0000000000001510. PMID: 28045774
de Sain-van der Velden MG, Diekman EF, Jans JJ, van der Ham M, Prinsen BH, Visser G, Verhoeven-Duif NM
Mol Genet Metab 2013 Sep-Oct;110(1-2):116-21. Epub 2013 Apr 13 doi: 10.1016/j.ymgme.2013.04.008. PMID: 23639448
Dykema DM
Adv Neonatal Care 2012 Feb;12(1):23-7. doi: 10.1097/ANC.0b013e318242df6d. PMID: 22301540

Clinical prediction guides

Janeiro P, Jotta R, Ramos R, Florindo C, Ventura FV, Vilarinho L, Tavares de Almeida I, Gaspar A
Eur J Pediatr 2019 Mar;178(3):387-394. Epub 2019 Jan 7 doi: 10.1007/s00431-018-03315-2. PMID: 30617651
Sood V, Rawat D, Khanna R, Sharma S, Gupta PK, Alam S, Sarin SK
J Pediatr Gastroenterol Nutr 2017 Jun;64(6):869-875. doi: 10.1097/MPG.0000000000001510. PMID: 28045774
de Sain-van der Velden MG, Diekman EF, Jans JJ, van der Ham M, Prinsen BH, Visser G, Verhoeven-Duif NM
Mol Genet Metab 2013 Sep-Oct;110(1-2):116-21. Epub 2013 Apr 13 doi: 10.1016/j.ymgme.2013.04.008. PMID: 23639448

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