Fatty Acid Oxidation Disorders

Carnitine Uptake Defect (CUD)

background

Carnitine uptake defect (CUD) is a condition that prevents the body from using fats for energy, particularly during periods without food (fasting). Carnitine, a natural substance acquired mostly through diet, is used by cells to process fats and produce energy. In people with CUD, proteins called carnitine transporters do not work properly. These proteins normally bring carnitine into cells and prevent the escape of carnitine from the body in urine. CUD is estimated to occur in less than 1 of 100 000 live births. However it has been reported to have an incidence rate of 1:40 000 live births in Japan.

clinical

Typically, initial signs and symptoms of this disorder occur during infancy or early childhood and often include changes in brain tissue (encephalopathy) resulting in functional abnormalities; an enlarged, poorly pumping heart (cardiomyopathy); confusion; vomiting; muscle weakness; and low blood sugar (hypoglycemia). Serious complications such as heart failure, liver problems, coma, and sudden unexpected death are also a risk. Severe illness due to CUD can be triggered by periods of fasting or illnesses such as viral infections, particularly when eating is reduced.

This condition is sometimes mistaken for Reye syndrome, a severe disorder that develops in children while they appear to be recovering from viral infections such as chicken pox or flu.

testing

Newborn screening using tandem mass spectrometry of a dried blood spot identifies low level of free carnitine (C0). (C0+C2+C3+C16+C18:1+C18)/Cit is also found as informative ratio. Plasma and urine carnitine analysis will reveal decreased free and total carnitine (C0) in plasma and overexcretion of carnitine in urine. The newborn’s mother should be investigated, as well, because several cases of maternal CUD have been identified following an abnormal newborn screening result in their offspring. Transporter assays and OCTN2 gene sequencing establish the diagnosis.

treatment

Treating CUD patients with oral L-carnitine supplementation is followed by a slow increase of plasma carnitine levels. If the infants’ levels reflect maternal primary carnitine deficiency, the rise in plasma levels is fast and this should prompt the work-up towards the diagnosis of maternal primary carnitine deficiency. CUD patients should also avoid fasting and sometimes low-fat, high carbonhydrate diet is used in addition to L-carnitine. Guidelines for the management of carnitine deficiency and other fatty acid mitochondrial disorders have been established.

Because the diagnosis and therapy of CUD is complex, the pediatrician is advised to manage the patient in close collaboration with a consulting pediatric metabolic disease specialist. It is recommended that parents travel with a letter of treatment guidelines from the patient’s physician.

inheritance

This disorder follows an autosomal recessive inheritance pattern. With recessive disorders affected patients usually have two copies of a disease gene (or mutation) in order to show symptoms. People with only one copy of the disease gene (called carriers) generally do not show signs or symptoms of the condition but can pass the disease gene to their children. When both parents are carriers of the disease gene for a particular disorder, there is a 25% chance with each pregnancy that they will have a child affected with the disorder.

Source: Newborn Screening Today (2011), PerkinElmer Inc., Waltham MA

Regional report

Some Governments need pushing for NBS in Middle East and North Africa

“Newborn screening is not simply buying a kit or a machine; it’s a whole approach of analysis and interpretation. Now, it’s time to convince the authorities to move forward”, says Dr. Issam Khneisser, NBS pioneer in the Middle East and North Africa (MENA) region.

Presentation

Expansion of the Dutch neonatal Screening Programme. Policy and Practice

In this presentation, the carefully crafted approach of shaping the innovation of the Dutch neonatal screening program is covered.

News

PerkinElmer Genetics Launches New LSD Testing Service

PerkinElmer® Genetics, located just outside of Pittsburgh, Pennsylvania, has been providing newborn screening services for over 20 years. During that time, the laboratory has processed close to six million samples using biochemical, molecular and mass spec based technology while partnering with the states of Pennsylvania, Mississippi, Nebraska, Louisiana and the District of Columbia. In 2010, PerkinElmer Genetics started offering a 6-plex assay to test for Gaucher, Niemann-Pick, Krabbe, Hurler-MPS-I, Pompe and Fabry lysosomal storage disorders. More recently, they completed the development and validation of tests for MPS-IVA and VI. Work is also underway to add testing for Adrenoleukodystrophy (X-ALD) with the goal to being able to offer all these tests as part of their StepOne® Newborn Screening, a “Lab in a Lab” or as back-up testing for labs that experience unplanned outages. For more information, please contact PJ Borandi at PJ.Borandi@PerkinElmer.com.

Regional report

Regional news: A report from North America

Newborn screening (NBS) expansion is once again gaining momentum in the United States with many disorders being considered due to promising new treatments, better testing methods and other factors that impact the decision making process. Three factors that have helped shape the NBS landscape in the U.S.

Interview

Taiwan on the forefront of implementing new disorders

Dr. Yin-Hsiu Chien, director of the newborn screening center at the National Taiwan University Hospital, has made diverse contributions in the field of inborn errors of metabolism and immunodeficiency. Her team, lead by Dr Wuh-Lang Hwu is devoted to the diagnosis and treatment of lysosymal storage diseases (LSD). Dr. Chien’s current work focuses on Pompe disease, specifically on early diagnosis and improvement of treatment. Dr. Chien and her team have played an important role in making Taiwan’s newborn screening programs into one of the most developed newborn screening programs in the world.

Presentation

NBS panel expansion in the Philippines, Maria Melanie Liberty B. Alcausin, MD, Philippines

The NBS Program in the Philippines started out as a pilot project involving 24 hospitals in the country’s capital region. It took some time for the newborn screening program to be successfully integrated into the national health program through the Philippine Newborn Screening Act of 2004. Almost two decades after the pilot project, the program was deemed ready for the expansion from screening for six disorders to screening for more than 20 disorders. The presentation from Dr. Melanie presents the challenges of implementing an expanded newborn screening program in a developing country like the Philippines and the conditions identified in the first phases of offering the service.

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