Journal of Clinical Neonatology

: 2015  |  Volume : 4  |  Issue : 4  |  Page : 275--277

Neonatal arrhythmias due to deficiency of carnitine palmitoyltransferase II

Annachiara Casadei1, Augusto Biasini1, Chiara Dalla Cuna1, Luciano Mancini2, Alberto Sensi3,  
1 Pediatric and Neonatal Intensive Care Unit, Cesena, Italy
2 Department of Pathological Anatomy, Bufalini Hospital, Cesena, Italy
3 Medical Genetics Unit, AVR, Pievesistina di Cesena, Cesena, Italy

Correspondence Address:
Annachiara Casadei
Department of Pediatrics, Neonatal Intensive Care Unit, Bufalini Hospital, Cesena


Carnitine palmitoyltransferase II (CPT II) deficiency is a rare disorder of mitochondrial fatty acid oxidation characterized by a multisystemic course and early death during the neonatal period. Early recognition and diagnosis are important because a prompt treatment at birth may prolong survival. In this case report, we detected and corrected hypoglycemia and severe hyperkalemia in a collapsed neonate who manifested early heart rate anomalies and myocardial hypertrophy on cardiac ultrasound rapidly followed by death. Multiorgan degeneration, mostly in the heart and liver, was revealed by autopsy. The tandem mass and molecular genetic testing confirmed the diagnosis of CPT II deficiency. Our data document and confirm the severity of the disease. Laboratories alterations such as hyperkalemia and hypoglycemia in a term neonate with myocardial hypertrophy must always alert the physician to investigate and treat the metabolic disease.

How to cite this article:
Casadei A, Biasini A, Cuna CD, Mancini L, Sensi A. Neonatal arrhythmias due to deficiency of carnitine palmitoyltransferase II.J Clin Neonatol 2015;4:275-277

How to cite this URL:
Casadei A, Biasini A, Cuna CD, Mancini L, Sensi A. Neonatal arrhythmias due to deficiency of carnitine palmitoyltransferase II. J Clin Neonatol [serial online] 2015 [cited 2022 Jun 29 ];4:275-277
Available from:

Full Text


Carnitine palmitoyltransferase II (CPT II) deficiency is a disorder of mitochondrial fatty acid oxidation in which long-chain acylcarnitines cannot be metabolized to carnitine and acyl-CoA, leading to accumulation of toxic long-chain acylcarnitines.

There are three distinct clinical entities of the disease; the neonatal form is the most severe and death is reported within few days to 6 months. Early recognition and diagnosis are important because a prompt treatment at birth may prolong survival.

We report a case of a newborn who presented a cardiac arrest and episodes of arrhythmias in the 1st day of life induced by the neonatal form of CPT II deficiency.

 Case Report

GH is a term female newborn delivered spontaneously after a normal pregnancy with good neonatal adaptation (Apgar score 8–10), an obstetric history of a positive group B strep test with incomplete prophylaxis and a previous history of several spontaneous abortions for fetal malformations (bilateral renal cystic dysplasia was found in two fetuses and an additive Dandy-Walker malformation was found in the second one).

On 2nd day, the baby developed an important generalized hypotonia, lethargy, and severe hypoglycemia; she was immediately admitted to Neonatal Intensive Care Unit and treated with glucagon and intravenous glucose with partial benefit, but 1 h after the admission she manifested an unexpected cardiac arrest that required endotracheal intubation, chest compression and adrenaline.

Blood tests showed normal inflammatory markers and hyperpotassemia that was corrected with bolus of calcium gluconate and insulin.

During the following days, the baby remained poorly reactive and developed a progressive clinical deterioration requiring mechanical ventilation. Laboratories studies showed progressive increase of transaminase, lactate dehydrogenase, creatine kinase and myoglobine and electrocardiogram revealed large T waves and prolonged QRS together with the evidence of a severe myocardial hypertrophy on cardiac ultrasound. The other investigations showed a bilateral hydronephrosis with mild compromission of renal function while head ultrasound was normal.

On 5th day, the baby presented repeated episodes of ventricular tachycardia treated with adenosine, the latest one went into ventricular fibrillation that didn't respond to defibrillation and adrenaline and followed by exitus.

Autopsy showed a severe cardiac hypertrophy of both ventricles, and a multiorgan degeneration due to fatty infiltration especially on the hearth, brain, liver, and kidneys. The tandem mass and molecular genetic testing confirmed the diagnosis of CPT II deficiency, in particular compound heterozygosity for two not previously described mutations in CPT2 gene were found: C.627_630dup (p. Pro211ValfsX24) and c.896_906dup (p. Arg303GlyfsXB), both can be considered pathogen.


The neonatal form of Carnitine Palmitoyl Transferase II Deficiency is the most severe form of the disease, in all the cases described in literature death occurred before 45 days, except in two cases in which prenatal diagnosis resulted in termination of pregnancy and in one case of a baby who survived until the age of 6 months because the antenatal diagnosis led to a prompt treatment that may have prolonged survival.[1]

Fasting in the early newborn period is indeed a main trigger of CPT II deficiency signs;[2] therefore, the current management consists of special formula that do not contain long-chain fatty acids but cover the need for essential fatty acids and provide a large fraction of calories as carbohydrates.

For these reasons, early diagnosis is important. Clinic and laboratories abnormalities should alert the physician to the possibility of the disease.

In our case, the baby showed a rapid deterioration of the clinical conditions by the 1st day of life in the presence of a myocardial hypertrophy that leaded to multiple episodes of arrhythmias and a cardiac arrest, together with the evidence of severe hypoglycemia and hyperpotassemia, the origin of which is probably due to the renal disease and the metabolic acidosis.

Cardiomegaly and cardiac arrhythmias are the most frequent manifestation of neonatal CPT II;[1],[3],[4] Hissink-Muller et al. reported data for 21 patients described in literature with neonatal CPT II and mentioned them respectively in 76% and 62% of the cases in literature. Kidneys are often involved and hallmarks of the early onset form could be also renal abnormalities such as cystic renal dysplasia, being reported in 54% of the patient, and metabolic crisis.[1],[5],[6] Dysmorphic features are also described such as long tapering fingers, hypoplastic toenails, microcephaly, agenesis of corpus callosum, polymicrogyria and cerebral calcifications.[6] Babies could appear lethargic and hypotonic soon after birth as in the present case.

Laboratories data should also be considered; remarkable features include hyperammonemia and hyperkalemia. In our case, the baby showed hyperpotassemia on the 2nd day of life that required treatment with calcium gluconate and insulin. We perform a research on Omim, the Online catalog of human genes and genetic disorders and we found that neonatal CPT II appears as the unique disease after have included the words cardiomegaly and hyperkalemia as matching terms; we detected furthermore that changing the matching terms with the words cardiomegaly and hypoglycemia, neonatal CPT II result as thefirst disease of the 13 identified.[7] Hypoglycemia is typically hypoketotic and these data are enough to suspect a disorder of fatty acid oxidation or ketogenesis.

We emphasize therefore that the early evidence of cardiac compromission together with laboratories alterations such as hyperkalemia and hypoglycemia could direct the diagnosis of the disorder, suggest the investigation of acylcarnitine in serum and set up a correct management. Tandem mass spectrometry that has revolutionized the diagnosis of fatty acid oxidation disorders is recommended as initial screening and has to be confirmed by detection of reduced CPT enzyme activity in muscle tissue. Molecular genetic testing of CPT II can confirm the diagnosis, and it is of particular importance for the management of the genetic risk in the family.[8]


The unvaluable collaborations of Dr. S. Ferdinandusse and Prof. Dr. R.J.A. Wanders (Academic Medical Center AMSTERDAM) for DNA and enzymatic analyses are acknowledged.

Source of Support:


Conflict of Interest:

None declared.


1Hissink-Muller P, Lopriore E, Boelen C, Klumper F, Duran M, Walther F. Neonatal carnitine palmitoyltransferase II deficiency: Failure of treatment despite prolonged survival. BMJ Case Rep 2009;2009:bcr02.2009.1550.
2Brucknerova I, Bzduch V, Behulova D, Ferianec V, Dubovicky M, Ujhazy E, et al. Reversible asphyxial status in a newborn due to neonatal form of carnitine palmitoyltransferase II deficiency. Neuro Endocrinol Lett 2008;29:627-30.
3Pierce MR, Pridjian G, Morrison S, Pickoff AS. Fatal carnitine palmitoyltransferase II deficiency in a newborn: New phenotypic features. Clin Pediatr (Phila) 1999;38:13-20.
4Sharma R, Perszyk AA, Marangi D, Monteiro C, Raja S. Lethal neonatal carnitine palmitoyltransferase II deficiency: An unusual presentation of a rare disorder. Am J Perinatol 2003;20:25-32.
5Distelmaier F, Vogel M, Spiekerkötter U, Gempel K, Klee D, Braunstein S, et al. Cystic renal dysplasia as a leading sign of inherited metabolic disease. Pediatr Nephrol 2007;22:2119-24.
6North KN, Hoppel CL, De Girolami U, Kozakewich HP, Korson MS. Lethal neonatal deficiency of carnitine palmitoyltransferase II associated with dysgenesis of the brain and kidneys. J Pediatr 1995;127:414-20.
7Online Mendelian Inheritance in Man: matching terms: 608836, Carnitine Palmitoyl transefrase II Deficiency, Lethal Neonatal.
8Sigauke E, Rakheja D, Kitson K, Bennett MJ. Carnitine palmitoyltransferase II deficiency: A clinical, biochemical, and molecular review. Lab Invest 2003;83:1543-54.