Carnitine Palmitoyltransferase II deficiency is an autosomal recessive metabolic defect of long chain fatty acids, that is characterized by an accumulation of these fatty acids in the body tissues, causing serious complications. Three different forms of CP2 Deficiency have been recognized. The lethal neonatal form is the most severe of these. Infants with this condition present with respiratory failure, seizures and coma, liver failure with hypoketotic hypoglycemia, and cardiac arrhythmias, within days of being born. Abnormalities in kidney and brain function may also be noticed. Rarely, the condition may also present with cerebral periventricular cysts and cystic dysplastic kidneys. The neonatal form of the disorder is extremely rare, having been described in a little more than 10 families worldwide.
As in most metabolic disorders, tandem mass spectrometric analysis is the preferred mode of detection. Initial screening involves detection of abnormal levels of long chain acylcarnitines in the serum. This in conjunction with reduced CPT2 enzyme activity and reduced serum concentrations of serum carnitine point to the condition. Genetic testing is also available, which can be used to check for mutations in the CPT2 gene. 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. This may require intermittent administration of glucose, avoiding fasting, and taking frequent meals. Other forms of management are secondary and depend upon the feature evinced. Prognosis for the neonatal form is extremely poor. Survival does not exceed more than a few months at most.
Al-Arrayed (Personal communication, Dubai, 2006) indicated that CPTII occurs in Bahrain at an approximate incidence of 1/10,000 births.
In a Moroccan family in which 4 sibs died from neonatal CPT II deficiency, Smeets et al. (2003) identified a novel splice site mutation in the CPT2 gene: a G-to-A transition in the splice acceptor site of intron 2. Studies at the mRNA level indicated that the affected children were homozygous for an insertion of a threonine at codon 534 (534insT) followed by a 25-bp deletion (bases 534-558). Studies of genomic DNA, however, revealed all patients were compound heterozygous for this 534insT/del25 mutation, and, on the other allele, for the novel splice site mutation. The findings underscored the incompleteness of mutation detection at the mRNA level in cases where a mutation leads to aberrant splicing or nonsense-mediated messenger decay.
In a study conducted by Joshi and Venugopalan (2007) over a seven year period (1998-2005), the clinical profiles of 166 neonates at high risk of having inborn errors of metabolism were evaluated by Tandem Mass Spectrometry (TMS). Out of a total of 38 neonates with positive TMS results, two babies (a male and a female; aged 2 and 18-days) were diagnosed with carnitine palmitoyltransferase-2 deficiency. Both patients presented with acute neonatal encephalopathy. Neither of the patients had consanguineous parents, although one of the patients had a family history of the condition.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Fatty acid oxidation disorders were diagnosed in 18/248 patients (7%) and were suffering enzymatic deficiency. The diagnosis was confirmed in all fatty acid oxidation disorders by measuring the enzyme activity in blood or skin fibroblasts. Four cases from a single family were found to have CPT II deficiency. The estimated incidence of this condition was 2 in 100,000 live births. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.