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Lethal Neonatal Carnitine Palmitoyl Transferase II Deficiency

CPT2


Presentation

  • Tandem mass spectrometry helped to clinch the diagnosis of CPT II Deficiency in the present case.[ncbi.nlm.nih.gov]
  • We present a three-day-old female child, admitted to us for lethargy, icterus, low sugars and convulsions.[ncbi.nlm.nih.gov]
Poor Feeding
  • Gradually hypotonia, lethargy, and poor feeding developed and by 20 hours of age recurrent cardiac dysrrhythmias, myocardial dysfunction, and renal insufficiency with intermittent hyperkalemia were apparent.[ncbi.nlm.nih.gov]
  • The early red flag signs raising suspicion of inborn errors are persistent/unexplained lethargy, vomiting, poor feeding, seizures, altered sensorium and failure to gain weight [ 5 ].[ncbi.nlm.nih.gov]
Poor Feeding
  • Gradually hypotonia, lethargy, and poor feeding developed and by 20 hours of age recurrent cardiac dysrrhythmias, myocardial dysfunction, and renal insufficiency with intermittent hyperkalemia were apparent.[ncbi.nlm.nih.gov]
  • The early red flag signs raising suspicion of inborn errors are persistent/unexplained lethargy, vomiting, poor feeding, seizures, altered sensorium and failure to gain weight [ 5 ].[ncbi.nlm.nih.gov]
Fatigue
  • Late-onset mitochondrial myopathies feature proximal muscle weakness, easy fatigueability, and variably elevated CK levels. Lactic acidemia is often absent.[the-rheumatologist.org]
  • ; Movement disorder; Seizure Weakness (65%) Severity: Usually mild; Occasionally severe or none Distribution: Proximal; Symmetric; Legs Arms; Paraspinal Course: Increases with age Other muscle features Muscle atrophy: May be generalized Fatigue with exercise[neuromuscular.wustl.edu]
  • Natelson, Association of medically unexplained fatigue with ACE insertion/deletion polymorphism in gulf war veterans, Muscle & Nerve, 30, 1, (38-43), (2004).[doi.org]
  • […] of nervous system morphology Hypoketotic hypoglycemia Cardiomegaly Hypothermia Heart block Ventricular arrhythmia Hyperkalemia Cerebral hemorrhage Hemivertebrae Plagiocephaly Hyperammonemia Unilateral renal agenesis Narrow palate Respiratory distress Fatigue[mendelian.co]
  • Pearls & Alerts for Treatment & Management Avoid factors causing physical stress Physical stress caused by illness, dehydration, fatigue, and, in some cases, high-fat diets can lead to acute decompensation.[medicalhomeportal.org]
Death in Infancy
  • The severe infantile form may lead to sudden death during infancy due, in general, to paroxysmal cardiac arrhythmias. The neonatal form is almost always lethal during the first months of life.[orpha.net]
  • […] in infancy: neonatal genetic screening may enable the prevention of sudden infant death Yuki Oshima, Takuma Yamamoto, Taisuke Ishikawa, Hiroyuki Mishima, Aya Matsusue, Takahiro Umehara, Takehiko Murase, Yuki Abe, Shin-ichi Kubo, Koh-ichiro Yoshiura,[nature.com]
  • Carnitine palmitoyltransferase 2 gene polymorphism is a genetic risk factor for sudden unexpected death in infancy.[ncbi.nlm.nih.gov]
Weight Gain
  • Case 3 A 7-year-old male presented for inpatient consultation with recurrent vomiting, metabolic acidosis, a 6-month history of exercise intolerance accompanied by weakness, and poor weight gain.[the-rheumatologist.org]
  • Poor feeding, poor weight gain, vomiting and diarrhea, lethargy, and hypotonia are initial symptoms.[genico.ch]
Jaundice
  • Some women carrying fetuses with Fatty Acid Oxidation Disorders have developed: excessive vomiting abdominal pain high blood pressure jaundice abnormal fat storage in the liver severe bleeding All women with a family history of CPT-2 deficiency should[newbornscreening.info]
  • They may experience neonatal jaundice and hemolysis that can be so serious as to cause neurologic damage or even death.[genico.ch]
Cardiomegaly
  • Clinical features include hypoketotic hypoglycemia, lethargy, seizures, hepatomegaly, liver dysfunction, cardiomegaly and dilated cardiomyopathy.[uniprot.org]
  • Keywords: Cardiomegaly, carnitine palmitoyltransferase II deficiency, hyperkalemia How to cite this article: Casadei A, Biasini A, Cuna CD, Mancini L, Sensi A. Neonatal arrhythmias due to deficiency of carnitine palmitoyltransferase II.[jcnonweb.com]
  • It is characterized by respiratory distress, seizures, altered mental status, hepatomegaly, cardiomegaly, cardiac arrhythmia, and, in many cases, dysmorphic features, renal dysgenesis, and migration defects. recessive.[uniprot.org]
  • Autopsy findings include diffuse lipid accumulation, cardiomegaly, dysplastic kidneys, and brain migration defects.[pediatricneurologybriefs.com]
  • He presented on the first day of life with nonketotic hypoglycemia, seizures, hepatomegaly, cardiomegaly with biventricular hypertrophy, and ventricular arrhythmias.[genome.jp]
Widely Spaced Nipples
  • spaced nipples ABDOMEN: [Liver]; Hepatomegaly; Macrovesicular steatosis; Lipid accumulation in hepatocytes; Liver calcifications; [Gastrointestinal]; Poor feeding GENITOURINARY: [Kidneys]; Enlarged polycystic kidneys (detectable prenatally); Dysplastic[genome.jp]
Bulbous Nose
  • Clinical Synopsis: INHERITANCE: Autosomal recessive HEAD AND NECK: [Head]; Microcephaly; [Face]; High, sloping forehead; Prominent forehead; [Eyes]; Cararacts; [Ears]; Overfolded helices; Low-set ears; Posteriorly-rotated ears; [Nose]; Bulbous nose; [[genome.jp]
  • nose 10 HP:0001640 Cardiomegaly 11 HP:0001640 Cardiomegaly hallmark 12 HP:0000518 Cataract NAMDC: Cataracts 13 HP:0002514 Cerebral calcification typical 14 HP:0008315 Decreased plasma free carnitine 15 HP:0011936 Decreased plasma total carnitine 16 HP[mseqdr.org]
  • nose Midface capillary hemangioma Clitoral hypertrophy Anal atresia Upper limb undergrowth Hypospadias Short thumb Proptosis Postnatal growth retardation Craniosynostosis Corneal opacity Low hanging columella 2-3 toe syndactyly Severe intrauterine growth[mendelian.co]
  • nose Microphthalmia Inguinal hernia Cerebral hemorrhage Recurrent respiratory infections Delayed skeletal maturation Coarctation of aorta Abnormality of the cardiovascular system Growth hormone deficiency Cardiomegaly Webbed neck Osteopenia Cavernous[mendelian.co]
High Sloping Forehead
  • Associated dysmorphic features were noted, including microcephaly, a high sloping forehead, overfolded helices, long and tapered fingers and toes, contractures, and hypoplastic toenails.[genome.jp]

Workup

  • Marked symmetrical weakness of both arms and legs was confirmed during the neurological workup. She was unable to raise her legs and had difficulties abducting her shoulders.[medicalbag.com]
  • The question remains of whether the male predominance is due to sex-related differences in exercise activities, an X-chromosomal modifier gene, or hormonal factors such as estrogen that seem to be a regulator of CPT. 17, 18 Diagnostic workup of exercise-induced[jamanetwork.com]
  • Workup Laboratory Studies If the patient is suspected of having primary carnitine deficiency or other metabolic disorders associated with secondary carnitine deficiency and is presenting with a metabolic emergency, the following studies are indicated:[emedicine.medscape.com]
  • Workup of such patients includes measuring plasma amino acids and looking for succinylacetone on urine organic acid analysis.[genico.ch]
Total Bilirubin Increased
  • bilirubin; Increased tissue levels of triglycerides; Increased tissue levels of free fatty acids; Severely decreased palmitate oxidation; Severely decreased carnitine palmitoyltransferase II (CPT II) activity (less than 10% of normal) in multiple tissues[genome.jp]

Treatment

  • Certain treatments may be advised for some children but not others. When necessary, treatment is usually needed throughout life. The following are treatments sometimes recommended for babies and children with CPT-2 deficiency: 1.[newbornscreening.info]
  • The Connecticut AIDS Drugs Assistance Program The CT AIDS Drug Assistance Program provides eligible low-income residents with medications and health insurance premium assistance for the treatment of HIV and HIV-related conditions.[ct.gov]
  • Heart Failure: Bench to Bedside presents a clear view of up-to-date approaches to clinical diagnosis and treatment, as well as offering insightful critiques of original and creative scientific thoughts on post-genomic HF research.[books.google.com]
  • The first line of treatment concentrates on providing a high carbohydrate and low fat diet, and methods to convert the toxic long chain fatty acids to harmless acylcarnitines.[cags.org.ae]
  • Treatment is primarily conservative for the infantile and the myopathic forms with high carbohydrate (70%) and low fat ( 2, 6, 8 ].[ncbi.nlm.nih.gov]

Prognosis

  • Prognosis for the neonatal form is extremely poor. Survival does not exceed more than a few months at most. Bahrain Al-Arrayed (2006) indicated that CPTII occurs in Bahrain at an approximate incidence of 1/10,000 births.[cags.org.ae]
  • Prognosis The myopathic form of CPT II has a good prognosis. The severe infantile form may lead to sudden death during infancy due, in general, to paroxysmal cardiac arrhythmias.[orpha.net]
  • Prognosis Prognosis is poor. The neonatal form is almost always lethal during the first months of life. The documents contained in this web site are presented for information purposes only.[orpha.net]
  • When diagnosed and treated AT BIRTH the prognosis for most of the FODs (i.e., MCAD etc) is excellent. Most can make adjustments to diet/meds when necessary during times of extra activity and illness and lead a full life.[fodsupport.org]
  • Even with treatment, the prognosis is very poor in these patients. Patients with the severe infantile form of CPT2 typically present within the first year of life.[invitae.com]

Etiology

  • Etiology The severe neonatal CPT II deficiency is caused by homozygous or compound heterozygous CPT2 mutations that typically result in complete loss of activity of the CPT II enzyme.[orpha.net]
  • Etiology More than 60 mutations in the CPT2 gene, resulting in general in amino acid substitutions or small deletions, cause the CPT II deficiency.[orpha.net]
  • Virus Detection The Virus Detection Section is responsible for: Provincial viral diagnostic services; Surveillance of respiratory, enteric and sexually transmitted infection of viral etiology; Supplying viral strain information and primary isolates to[gov.mb.ca]
  • Presence or absence of an anion gap (AG) can help to distinguish the underlying etiology. In general, with a pure or uncompensated metabolic acidosis, every 10 mEq/L fall in bicarbonate (HCO 3 ) results in an average pH fall of 0.15.[mhmedical.com]
  • The molecular etiologies of these syndromes have not been determined. In this investigation, we considered the hypothesis that these syndromes result from defective transport of carnitine into tissues, particularly skeletal muscle.[osti.gov]

Epidemiology

  • Summary Epidemiology It is a rare form of CPT II deficiency that has been reported in less than 20 families.[orpha.net]
  • Summary Epidemiology More than 300 CPT II cases have been described with the myopathic form being the most common (myopathic form: 86%, severe infantile form: 8%, neonatal form: 6% of cases).[orpha.net]
  • Cerevisiae, homolog of (FLAD1; FADS) ; Chromosome 1q21.3; Recessive Epidemiology: 9 patients Genetics Mutations: Biallelic, Frameshift, Missense or 1 amino acid deletion Mutation locations Molybdopterin binding (MPTb) domain, upstream of FADS domain:[neuromuscular.wustl.edu]
  • Am J Hum Genet 75:97–105 PubMedCentral PubMed CrossRef Google Scholar Schaefer AM, Taylor RW, Turnbull DM, Chinnery PF (2004) The epidemiology of mitochondrial disorders – past, present and future.[link.springer.com]
  • Genetic epidemiology of the carnitine transporter OCTN2 gene in a Japanese population and phenotypic characterization in Japanese pedigrees with primary systemic carnitine deficiency. Hum Mol Genet. 1999 Nov. 8(12):2247-54. [Medline].[emedicine.medscape.com]
Sex distribution
Age distribution

Pathophysiology

  • Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test Carnitine palmitoyltransferase II (CPT II) deficiency is an autosomal recessive disorder of long-chain fatty-acid oxidation.[mayomedicallaboratories.com]
  • The syndrome of rhabdomyolysis: Pathophysiology and diagnosis. Eur. J. Intern. Med. 2007, 18, 90–100. [ Google Scholar ] [ CrossRef ] [ PubMed ] Zutt, R.; van der Kooi, A.J.; Linthorst, G.E.; Wanders, R.J.; de Visser, M.[mdpi.com]
  • Simon E Olpin, Pathophysiology of fatty acid oxidation disorders and resultant phenotypic variability, Journal of Inherited Metabolic Disease, 36, 4, (645-658), (2013).[doi.org]
  • Pathophysiologic findings The CPT system mediates the transport of long-chain fatty acids into the mitochondrial matrix.[jamanetwork.com]
  • Pharmacological and pathophysiological roles of carnitine/organic cation transporters (OCTNs: SLC22A4, SLC22A5 and Slc22a21). Biopharm Drug Dispos. 2012 Sep 5. [Medline]. Koizumi A, Nozaki J, Ohura T, et al.[emedicine.medscape.com]

Prevention

  • More on Carnitine palmitoyltransferase II deficiency » Elbow flexion contracture : Summary A chronic loss of elbow joint motion due to structural changes in muscle, tendons, ligaments, or skin that prevent normal movement of the joints of the elbow. 2[familydiagnosis.com]
  • Muscle effects can include: muscle aches cramps weakness reddish-brown urine If muscle symptoms occur, prompt treatment is needed to prevent kidney damage.[newbornscreening.info]
  • From Wikidata Jump to navigation Jump to search lipid metabolism disorder characterized by an enzymatic defect that prevents long-chain fatty acids from being transported into the mitochondria CPT-II infantile carnitine palmitoyltransferase II deficiency[wikidata.org]
  • This can prevent low blood sugar. It can also prevent the body using fats for energy. And you should stay away from things that may trigger symptoms. These may include skipping meals, exposure to cold, stress, and a lot of exercise.[cedars-sinai.org]
  • Muscle effects can include: • muscle aches • cramps • weakness • reddish-brown urine If muscle symptoms occur, prompt treatment is needed to prevent kidney damage.[checkorphan.org]

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