JCDR - Register at Journal of Clinical and Diagnostic Research
Journal of Clinical and Diagnostic Research, ISSN - 0973 - 709X
Paediatrics Section DOI : 10.7860/JCDR/2018/29861.11164
Year : 2018 | Month : Feb | Volume : 12 | Issue : 02 Full Version Page : SR01 - SR03

A Clinical and Biochemical Camouflage-Carnitine Palmitoyltransferase-1 Deficiency: A Case Series

Shrikiran Hebbar1, Sowmya Shashidhara2, Suneel Mundkur3, Shravan Kanaparthi4

1 Professor and Head, Department of Paediatrics, Kasturba Medical College, Manipal, Karnataka, India.
2 Assistant Professor, Department of Paediatrics, Kasturba Medical College, Manipal, Karnataka, India.
3 Additional Professor, Department of Paediatrics, Kasturba Medical College, Manipal, Karnataka, India.
4 Senior Resident, Department of Paediatrics, Kasturba Medical College, Manipal, Karnataka, India.

NAME, ADDRESS, E-MAIL ID OF THE CORRESPONDING AUTHOR: Dr. Sowmya Shashidhara, Assistant Professor, Department of Paediatrics, Manipal Academy of Higher Education, Manipal-576104, Karnataka, India.
E-mail: sowmyashashidhara86@gmail.com

Carnitine Palmitoyltransferase-1 (CPT-1) deficiency is a rare metabolic disorder of fatty acid oxidation. The presentation of this deficiency is a mixed bag of several clinical and biochemical manifestations which is determined by the tissue-specific isoforms of the enzyme. Presenting in one way, which can be lethal due to cardiac complications, another way that this disorder can come to a clinician’s attention is when children manifests with increasing lethargy during intercurrent illnesses. Rarely, but not exclusively, a seizure may be the only presenting complaint along with severe metabolic acidosis. In this case series, we present a discussion of three cases with CPT1 deficiency presenting with a camouflage of various contrasting clinical and biochemical manifestations.


Case 1

A 2.5-year-old boy was brought to outpatient of our Paediatric Department with complaints of increasing lethargy after an episode of loose stools lasting for the previous three days. There were similar episodes of lethargy during minor illnesses since, he turned 16 months. During one of these illnesses a random blood sugar performed was 22 mg/dL for which he was treated at 14 months of age in a primary care health centre. Birth history was unremarkable with age appropriate development and immunisation. There was consanguinity among parents. The sibling of this child was healthy and had an average acylcarnitine profile. On examination, he was underweight and stunted, the Glasgow Coma Scale was 15/15. Pulse-106/minutes, respiratory rate–22/minutes, BP-86/60 mmHg. Abdominal examination showed firm hepatomegaly of 6 cm with smooth margins. There was no splenomegaly. There were no signs of meningeal irritation. The cardiovascular and respiratory system examination were healthy. The investigations done are outlined in [Table/Fig-1]. He was treated with intravenous dextrose, and normal saline, vitamins B1, B2, and B6. He recovered after a week, but liver enzymes remained elevated ALT-110 IU/L, AST-167 IU/L. Parents were advised to initiate a carbohydrate-rich diet during intercurrent illnesses. The child remained underweight on follow up but otherwise was healthy.

Comparative features of the cases in our series.

Clinical featuresCase 1Case 1Case 1
Presenting featureDrowsiness, unconsciousness, lethargy, seizures, hypoglycaemia with concurrent illnesses since 1.5 years of ageVomiting, lethargy and fast breathing for three daysVomiting, irritability, seizures
Maternal historyHypertensive mother, developmental delay, consanguinity,Primigravida, no antenatal complicationsHistory of one abortion and one sibling death
Birth weight in kgThree3.22.75
Presented at2.5 yearsThree months1.5 months
Preceding illnessAcute gastroenteritisCough, cold and coryza 15 days before admissionCough and nasal discharge
Laboratory investigations with normal values
Creatinine (0.5–0.9 mg/dL)
Sodium (135-145 mEq/L)132128128
Potassium (3.5-5.5 mEq/L)4>75.8
Calcium (9-11 mg/dL)
Ammonia (11-35 μg/dL)9695183
Lactate (5-21 mg/dL)15.614134
Pyruvate (0.7-1.4 mg/dL)0.590.70.7
1AST (10-45 IU/L)1516931
2ALT (12-45 IU/L)1352521
3ALP (145-420 IU/L)268254238
4CRP (0-10 mg/L)0.30.96
5RBS (<200 mg/dL)2211895
6CSF examinationNot doneNot doneNormal
Haemoglobin (10.5-15 mg/dL)8.38.412.7
Total white cell count (4.0-14.0*10.3 cells/mm3)1500015,1006600
Platelet (150-400*10.3 cells/mm3)356000533000695000
Urea (7-18 mg/dL)121218
Direct bilirubin (<1 mg/dL)
Indirect bilirubin (mg/dL)
Serum albumin (3.5-5.0 mg/dL)4.783.423.7
Triglycerides (<150 mg/dL)837656
Prothrombin time (9.5-13.5 seconds)13.915.916.8
Activated partial prothrombin time (30-40 seconds)23.620.822
7INR (<1.1)
Chloride (98-106 mEq/L)9883.2104
Creatine phosphokinase 5-130 (IU/L)33338108
Urine proteinNegativeNegative+1
Urine sugar (mg/dL)NegativeNegative+1
Urine ketone+1Negative+1
pCO2 mm of Hg24.723.315.9
pO2 mm of Hg124106138
HCO2 (mEq/L)
Base excess61428.3
Anion gap18.524.227.7
Chest X-rayNormalCardiomegaly, clear lung fieldsNormal
Ultrasound AbdomenHepatomegaly with coarse echotextureNormalNormal
2D Echo testNormalSevere PAH, right ventricular dysfunction and dilatation.Normal
C0/(C16+C18) ratio1510.3238.2230.4
Total carnitine (normal–20-87.7)239.7308.69555.1
Free carnitine (normal–24.7-66.6)211.44235.82536.7
Methyl malonic acidNot detectedNot detectedNot detected
Urinary orotic acidNot detectedNot detectedNot detected
TreatmentIntravenous dextrose, rehydration therapyIntravenous fluids, Dextrose, dobutamine, adrenaline, carnitine, milrinoneBicarbonate, dopamine, cephalosporin, antiepileptic, multivitamins-B1,B2,B6 ventilation

1Aspartate transaminase, 2Alanine transaminase, 3Alkaline phosphatase, 4C-reactive Protein, 5Random blood sugar, 6Cerebrospinal fluid, 7International Normalized Ratio

Case 2

A 3-month-old girl was seen in the emergency room for repeated vomiting of feeds and, fast breathing developing over three days. She had an acute respiratory illness 15 days prior and received outpatient treatment. Her birth history was unremarkable. She had attained partial head control and social smile and had no significant family history. On examination, pulse-170/minutes, BP: 84/58 mmHg, respiratory rate–68/minutes, Capillary Filling Time- >5 seconds, pulse poorly felt. The respiratory system showed intercostal and subcostal retractions and bilateral fine crackles. Cardiovascular system examination revealed apex in fifth intercostal space, and loud heart sounds with an audible S3. No murmurs were heard. Abdomen examination revealed a liver size of 6.5 cm below costal margin. The neurological systemic was normal. Investigations are outlined in [Table/Fig-1]. She was managed with oxygen and ventilator support, intravenous fluids, dextrose, inotropic support with dobutamine, adrenaline, and intravenous sodium bicarbonate. Oral Sildenafil at a dose of 3 mg/kg/day in three divided doses was given for pulmonary hypertension. She succumbed after five days of ICU care.

Case 3

A 45-day-old boy was brought with persistent vomiting for two weeks and generalised seizures. He had cough and coryza a week before. The birth history was unremarkable. Maternal history showed one previous spontaneous abortion and one sibling death due to unexplained metabolic acidosis and ketonuria. On examination, he had tachycardia and tachypnoea. Neurological examination revealed a petulant child. There were no focal neurological deficits. Respiratory system and cardiovascular system examination were unremarkable. On palpation of the abdomen, liver measured 3.5 cm below the costal margin. Investigations are outlined in [Table/Fig-1]. He was managed in intensive care with intravenous dextrose, antiepileptics. Metabolic acidosis was corrected with intravenous sodium bicarbonate. During hospitalisation, he was ventilated due to uncontrolled seizures. He was started on carbohydrate rich diet, vitamins B1, B2, B6, and antiepileptics. At six month follow up, he was seizure free and developmentally normal. There was no history of exogenous carnitine supplementation in any of the above-described cases.


Carnitine palmitoyltransferase-1 deficiency is a rare disorder of oxidation of fatty acids [1]. Three isoforms of CPT-1 have been described–CPT1a; associated with activity predominantly in the liver, CPT1b; muscle specific isoenzyme, CPT1c; brain-specific activity [2-4]. The Hutterite population distributed across the United States and Canada is known to be associated with this rare, autosomal recessive disorder [5,6]. The clinical presentations of reduced enzyme activity predominantly involve hepatic, muscle and neurological systems. Hepatic manifestations due to deficiency of CPT1a are usually seen between birth to 18 months of age, where affected children develop lethargy and hypoglycaemia, following antecedent illnesses. The evaluation shows elevated liver enzymes and fatty acids [7]. A case of CPT1 deficiency which manifested in an adolescent boy has been reported in India which presented with hepatic encephalopathy [8]. Though, the exact prevalence of CPT deficiency is not knwn, CPT1 deficiency accounts for 5% of fatty acid oxidation defects according to a study done in 2013 by a tertiary care centre in Delhi [9]. The first case in our series manifested similarly along with a metabolic acidosis with an anion gap of 18. The muscle isoform CPT1b is predominantly expressed in the heart CPT1b deficiency is known to cause lipotoxicity in the heart during pathological stress, aggravating underlying cardiac pathology [4]. In line with this, the patient in case second presented similarly with cardiogenic shock, dilatation of ventricles and severe metabolic acidosis and elevated total/free carnitine ratio and acylcarnitine. The neuronal isoform of CPT1c is localised in the hypothalamus, amygdala, and hippocampus [10]. A reduced function of this isotype has been, observed in recent studies in mice, shown to be associated with motor impairment and hypoactivity [3]. The third case in this series manifested with lethargy, poor suck, seizures and encephalopathy similar to that described in the deficient isoform CPT1c but on the other hand, these features may not be exclusive to the disease in question.

The diagnosis of a disorder of fatty acid oxidation in the above clinical settings is usually entertained when certain pointers are present in the blood metabolic work up like metabolic acidosis with a high anion gap, with either an elevated or normal ammonia levels as described in our cases. Tandem mass spectroscopy for acylcarnitine profile is highly specific for fatty acid disorders [11]. In CPT-1 deficiency, elevated free carnitine concentrations and low acylcarnitine concentrations are diagnostic findings [12]. An elevated C0/(C16+C18) ratio >100 has been described in CPT-1 deficiency and is specific as outlined by the referenced studies [13]. Likewise, the most sensitive indicator to diagnose CPT-2 deficiency is an elevated (C16+C18:1)/C2 ratio [13,14]. In the cases described in our series, there is an elevation of the C0/(C16+C18) ratio of 1510.3, 238.2 and 230.4 in cases first, second and third, respectively, which is greater than the typical cut-offs. Several mutations in the CPT1 gene are described till date, and mutational analysis is recommended for the definitive diagnosis [6,15]. Alternatively, the enzyme activity of CPT1 assayed by tandem mass spectroscopy in cultured fibroblasts can be implemented to confirm the diagnosis [16]. In the three described cases in our series, a mutational analysis was not possible in one case as the child died very early during the treatment despite our best efforts. The other two children described were offered the mutation analysis but was not done due to financial constraints and limited resource settings.

Treatment for deficiency of CPT1 entails a low-fat diet augmented with medium-chain triglycerides, carnitine supplements, and avoidance of fasting and sustained exercise [7]. Prenatal diagnosis is offered to families along with newborn screening with tandem mass spectroscopy [17]. The outcome of this disorder is lethal in many cases causing sudden deaths, arrhythmias, and failure to thrive in children [18]. In our experience with these cases, two children have survived but remained underweight, though developmentally appropriate. One child expired due to cardiac and renal complications. The sibling screen for one child was healthy. Prenatal screening was offered to the parents of all the cases.


Carnitine Palmitoyltransferase-1 deficiency is a rare disorder presenting as a camouflage of varying manifestations clinically and biochemically. Tandem mass spectroscopy for C0/(C16+C18) ratios in cases with a high-index of suspicion is precise and can be used to identify these cases. Treatment is supportive, and prenatal diagnosis can be offered to families with affected children.

1Aspartate transaminase, 2Alanine transaminase, 3Alkaline phosphatase, 4C-reactive Protein, 5Random blood sugar, 6Cerebrospinal fluid, 7International Normalized Ratio


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