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What is Systemic primary carnitine deficiency and explain in detail?
Systemic primary carnitine deficiency (SPCD)  is an inborn error of fatty acid transport caused by a defect in the transporter responsible for moving carnitine across the plasma membrane. Carnitine is an important amino acid for fatty acid metabolism. When carnitine cannot be transported into tissues, fatty acid oxidation is impaired, leading to a variety of symptoms such as chronic muscle weakness, cardiomyopathy, hypoglycemia and liver dysfunction.  The specific transporter involved with SPCD is OCTN2, coded for by the SLC22A5 gene located on chromosome 5.  SPCD is inherited in an autosomal recessive manner, with mutated alleles coming from both parents.
Acute episodes due to SPCD are often preceded by metabolic stress such as extended fasting, infections or vomiting.  Cardiomyopathy can develop in the absence of an acute episode, and can result in death.  SPCD leads to increased carnitine excretion in the urine and low levels in plasma.  In most locations with expanded newborn screening, SPCD can be identified and treated shortly after birth.  Treatment with high doses of carnitine supplementation is effective, but needs to be rigorously maintained for life.

Signs and symptoms
The presentation of patient with SPCD can be incredibly varied, from asymptomatic to lethal cardiac manifestations.  Early cases were reported with liver dysfunction, muscular findings (weakness and underdevelopment), hypoketotic hypoglycemia, cardiomegaly, cardiomyopathy and marked carnitine deficiency in plasma and tissues, combined with increased excretion in urine.  Patients who present clinically with SPCD fall into two categories, a metabolic presentation with hypoglycemia and a cardiac presentation characterized by cardiomyopathy.  Muscle weakness can be found with either presentation.In countries with expanded newborn screening, SPCD can be identified shortly after birth.  Affected infants show low levels of free carnitine and all other acylcarnitine species by tandem mass spectrometry.  Not all infants with low free carnitine are affected with SPCD.  Some may have carnitine deficiency secondary to another metabolic condition or due to maternal carnitine deficiency.  Proper follow-up of newborn screening results for low free carnitine includes studies of the mother to determine whether her carnitine deficiency is due to SPCD or secondary to a metabolic disease or diet.  Maternal cases of SPCD have been identified at a higher than expected rate, often in women who are asymptomatic.  Some mothers have also been identified through newborn screening with cardiomyopathy that had not been previously diagnosed.  The identification and treatment of these asymptomatic individuals is still developing, as it is not clear whether they require the same levels of intervention as patients identified with SPCD early in life based on clinical presentation.

Genetics
SPCD is an autosomal recessive condition, meaning a mutated allele must be inherited from each parent for an individual to be affected.  The gene responsible for the OCTN2 carnitine transporter is SLC22A5, located at 5q31.1-32.  SLC22A5 is regulated by peroxisome proliferator-activated receptor alpha.  The transporter, OCTN2, is located in the apical membrane of the renal tubular cells, where it plays a role in tubular reabsorption.The defective OCTN2 is unable to recapture carnitine prior to its excretion in urine, leading to the characteristic biochemical findings of massively increased urine carnitine levels and significantly decreased plasma carnitine levels.  Decreased levels of plasma carnitine inhibit fatty acid oxidation during times of excessive energy demand.  Carnitine is needed to transport long chain fatty acids into the mitochondria, where they can be broken down to produce acetyl-CoA.  Individuals with SPCD cannot produce ketone bodies as energy due to the interruption of fatty acid oxidation.  Although SPCD is an autosomal recessive condition, heterozygotes have been shown to be at an increased risk for developing benign cardiomyopathy compared to wild type individuals.

Diagnosis
The first suspicion of SPCD in a patient with a non-specific presentation is an extremely low plasma carnitine level.  When combined with an increased concentration of carnitine in urine, the suspicion of SPCD can often be confirmed by either molecular testing or functional studies assessing the uptake of carnitine in cultured fibroblasts.

Treatment
Identification of patients presymptomatically via newborn screening has allowed early intervention and treatment.  Treatment for SPCD involves high dose carnitine supplementation, which must be continued for life.  Individuals who are identified and treated at birth have very good outcomes, including the prevention of cardiomyopathy.  Mothers who are identified after a positive newborn screen but are otherwise asymptomatic are typically offered carnitine supplementation as well