Christiane Theda MD PhD (FMH and Melbourne, Australia)

1. Introduction to the ALD Newborn Screening Study to be performed at Frederick Memorial Hospital and three other Maryland Hospitals PART 1: BACKGROUND INFORMATION Christiane Theda MD PhD (FMH and Melbourne, Australia) Presenters: Pam Bell RNC, Clinical Educator, FMH NICU and Janice Lane RN, Clinical Educator, FMH FC/Peds TO RETURN TO WEB PAGE – click here

2. Adrenoleukodystrophy (ALD) is an inherited disorders (X-linked recessive inheritance – typically mothers inherit the disease to their sons). ALD can manifest at different ages with different forms of the disease. Estimated disease frequency is 1 in 21,000 males. TO RETURN TO WEB PAGE – click here

3. Most common is the childhood cerebral form of ALD: Behavior changes and loss of motor, auditory and visual function are appearing typically between age 4 and 10 years. Symptoms are due demyelination – the destruction of myelin, a substance essential for brain function. (Lorenzo in the movie “Lorenzo’s Oil” was affected by this form of ALD) TO RETURN TO WEB PAGE – click here

4. Other forms of ALD are: An adult form with loss of motor function due to a peripheral neuropathy (Adrenomyeloneuropathy). Disturbance of adrenal gland function (adrenal insufficiency or Addison’s disease) is another manifestation of ALD (children or adults). TO RETURN TO WEB PAGE – click here

5. Other forms of ALD: Sometimes a female carrying the ALD gene (female heterozygote) has symptoms (usually as adult). Very rarely, a male carrying the gene has no symptoms, even up to old age. TO RETURN TO WEB PAGE – click here

6. Diagnosis of ALD: ALD can be diagnosed by a blood test which analyses the levels of very long chain fatty acids (VLCFA). VLCFA accumulate in blood due to the underlying genetic defect. TO RETURN TO WEB PAGE – click here

7. Other diseases with elevated VLCFA: Peroxisomal disorders (PD) - a group of disorders that are related to ALD due to the nature of the defects. Some patients with PD may be quite ill (floppy, seizures) and could be patients in a NICU. Both peroxisomal disorders and ALD affect the assembly and/or function of a cell organelle called the peroxisome. TO RETURN TO WEB PAGE – click here

8. Newborn Screening for ALD and PD: Why would we want to screen newborns for ALD and PD? Diet therapy is now commonly used and studies indicate that it may positively affect outcome (usually severe and debilitating loss of function and ultimately death) when started early. TO RETURN TO WEB PAGE – click here

9. Newborn Screening for ALD and PD: Why would we want to screen newborns for ALD and PD? Early diagnosis can lead to early evaluations (such as MRI detection of demyelination before frank symptoms or endocrine testing before dangerous adrenal insufficiency develops). TO RETURN TO WEB PAGE – click here

10. Newborn Screening for ALD and PD: Why would we want to screen newborns for ALD and PD? Early diagnosis and evaluations will leave time to assess if other therapies may be beneficial to individual patients (such as bone marrow / hematopoietic stem cell transplants). TO RETURN TO WEB PAGE – click here

11. Newborn Screening for ALD and PD: Why would we want to screen newborns for ALD and PD? Reproductive choices for parents (knowing about the potential risk of other affected children allows for informed choices for family planning; also, prenatal diagnosis for ALD / PD is available). TO RETURN TO WEB PAGE – click here

12. Newborn Screening for ALD and PD: Why have we not been screening newborns for ALD and PD until now? New technology (tandem mass spectrometry) has developed over the last few year and is now used for routine newborn screening. TO RETURN TO WEB PAGE – click here

13. Newborn Screening for ALD and PD: Tandem mass spectrometry: Allows high throughput testing using the routine blood spots for a great number of different disorders. A method to screen for elevated VLCFA has been developed. TO RETURN TO WEB PAGE – click here

14. Newborn Screening for ALD and PD: Preliminary studies: Yes, using the new method, patients later diagnosed with elevation of VLCFA with the “old fashioned” blood test had elevated VLCFA at birth when their newborn screening blood cards were analyzed retrospectively– very encouraging! TO RETURN TO WEB PAGE – click here

15. Newborn Screening for ALD and PD: So, here we are: Frederick Memorial Hospital has been included as one of four Maryland Hospitals to perform a prospective study to offer optional testing for ALD / PD to parents. The other three hospitals are: Johns Hopkins Hospital, Johns Hopkins Bayview Medical Center and GBMC in Towson TO RETURN TO WEB PAGE – click here