Christiane Theda MD PhD (FMH and Melbourne, Australia)

Introduction to the Introduction to the ALD Newborn ALD Newborn Screening StudyScreening Study to be performed to be performed at at Frederick Memorial HospitalFrederick Memorial Hospital and three other Maryland and three other Maryland HospitalsHospitalsPART 1: BACKGROUND PART 1: BACKGROUND INFORMATIONINFORMATIONChristiane Theda MD PhD Christiane Theda MD PhD (FMH and Melbourne, (FMH and Melbourne, Australia)Australia) Presenters: Presenters: Pam Bell RNC, Clinical Educator, FMH Pam Bell RNC, Clinical Educator, FMH NICU and Janice Lane RN, Clinical Educator, FMH NICU and Janice Lane RN, Clinical Educator, FMH FC/PedsFC/Peds

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http://www.ctheda.org/B-ALDStudy-Main.html

Adrenoleukodystrophy (ALD)Adrenoleukodystrophy (ALD) is is an inherited disorders (X-linked an inherited disorders (X-linked recessive inheritance – typically recessive inheritance – typically mothers inherit the disease to mothers inherit the disease to their sons).their sons).ALD can manifest at ALD can manifest at different different agesages with with different formsdifferent forms of the of the disease. disease. Estimated disease Estimated disease frequencyfrequency is 1 is 1 in 21,000 males.in 21,000 males.



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


Other formsOther forms of ALD are: of ALD are: An An adult formadult form with loss of motor with loss of motor function due to a peripheral function due to a peripheral neuropathy neuropathy ((Adrenomyeloneuropathy).Adrenomyeloneuropathy).Disturbance of adrenal gland Disturbance of adrenal gland function (function (adrenal insufficiencyadrenal insufficiency or or Addison’s disease) is another Addison’s disease) is another manifestation of ALD (children or manifestation of ALD (children or adults).adults).



Other formsOther forms of ALD: of ALD: Sometimes a female carrying the Sometimes a female carrying the ALD gene (female heterozygote) ALD gene (female heterozygote) has symptoms (usually as adult).has symptoms (usually as adult).Very rarely, a male carrying the Very rarely, a male carrying the gene has no symptoms, even up to gene has no symptoms, even up to old age.old age.



Diagnosis of ALD:Diagnosis of ALD: ALD can be diagnosed by a blood ALD can be diagnosed by a blood test which analyses the levels of test which analyses the levels of very long chain fatty acidsvery long chain fatty acids (VLCFA).(VLCFA).

VLCFA accumulate in blood due to VLCFA accumulate in blood due to the underlying genetic defect.the underlying genetic defect.



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


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



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



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



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


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


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


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

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

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Christiane Theda MD PhD (FMH and Melbourne, Australia)