Perceptions and Experiences of Families of Infants Diagnosed with X-Linked Adrenoleukodystrophy (X-ALD) via Newborn Screening in Georgia and Kentucky

Abstract

Introduction:

Newborn screening (NBS) for X-linked adrenoleukodystrophy (X-ALD) was added to the Recommended Uniform Screening Panel (RUSP) in 2016 to enable early diagnosis and treatment. This study aimed to understand the experiences of parents/caregivers of children with X-ALD to improve the NBS process and referral to appropriate clinicians.

Methods:

Parents/caregivers were recruited through NBS coordinators and genetic counselors in 6 states. Semi-structured interviews were conducted via Zoom. Two coders independently coded transcripts using MAXQDA software, and thematic analysis was conducted.

Results:

Four mothers and 3 fathers (for a total of 4 affected children) were interviewed. Before NBS, some parents were unaware of the purpose of the heel prick test. During the screening process, parents expressed mixed emotions of confusion, anxiety, and fear. Most lacked understanding of X-ALD and did not like the way the information was disclosed. All were referred to genetics and had positive feedback on this interaction. All were followed by endocrinology and neurology. Barriers included lack of access to clinics during the COVID-19 pandemic and lack of PCPs’ knowledge about X-ALD.

Conclusion:

Overall, parents were grateful for NBS but expressed concerns about the medicalization of their children’s childhood. The referral process is divided into 3 stages: screening, diagnostic, and treatment/management. Parents had both positive and negative feedback at various points in the referral process. Study results will help improve the NBS referral process in the Southern US and have implications for other locations that may choose to add X-ALD to their NBS programs in the future.

Introduction

X-Linked Adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by pathogenic variants in the ABCD1 gene. ¹ The historical prevalence when heterozygous females are included is estimated at 1 in 17,000. ² ABCD1 codes for ATP-binding cassette protein (ALDP) that is involved in the transport of very long chain fatty acids (VLCFAs) to the peroxisome for β-oxidation. When this gene does not function properly, VLCFAs, specifically C:26, accumulate in the adrenal glands and in the myelin surrounding the nerve cells in the brain and spinal cord. ³ Symptoms of X-ALD can be progressive and variable. The 3 common presentations in males are cerebral disease, adrenomyeloneuropathy (AMN) and adrenal insufficiency. Females with X-ALD rarely develop cerebral disease or adrenal insufficiency, but many develop adrenomyeloneuropathy in later years.^{4 -6}

The most severe presentation of X-ALD, the cerebral form, is characterized by cerebral demyelination and rapid decline. The average age of onset of this form is 7 years. ² Affected individuals may present with cognitive deficits initially presenting as attention deficit hyperactivity disorder (ADHD), aggressive behavior, muscle weakness, and seizures. ⁷ The prognosis of cerebral ALD is very poor. ⁸ Without life-saving treatment of hematopoietic stem cell transplantation or autologous gene therapy, these problems can worsen quickly and cause death. ⁹ Some males and females with X-ALD develop a milder presentation of X-ALD known as adrenomyeloneuropathy (AMN). AMN symptoms most frequently occur in the third or fourth decade of life. These individuals present with neurologic symptoms such as spastic paraparesis and sensory ataxia with or without adrenal insufficiency. ¹⁰ The third common presentation in males with X-ALD is isolated adrenocortical insufficiency. X-ALD males can have adrenal insufficiency without neurological symptoms. This can present within the first year of life; thus, male babies with X-ALD should be followed life-long by endocrinology after the NBS diagnosis of XALD has been confirmed.^11,12

Newborn screening (NBS) is a public health service conducted to identify newborns with serious but actionable conditions. Its purpose is to detect these conditions early enough to begin treatment, which reduces or even eliminates the effect of the condition. In the United States (US), the Recommended Uniform Screening Panel (RUSP) is a list of disorders that the Department of Health and Human Services (DHHS) recommends for states to screen as part of their state NBS programs. Each state decides which conditions will be included in their NBS programs resulting in variability between states regarding which disorders are screened at birth. NBS for X-ALD was added to the RUSP in 2016. ⁵ In the southern US, Florida, Tennessee, and Kentucky added X-ALD to their state’s NBS programs in 2018. Texas started screening in 2019. Georgia started screening in 2020 and North Carolina in 2021.^13,14

For NBS, the sample is collected through a heel prick at the hospital and a dried blood spot is sent to the laboratory. If the results are abnormal, the laboratory personnel will contact the NBS coordinators, and both the primary care physicians (PCPs) and genetics team will be notified. The PCP then informs the family of the screening results and orders a second round of blood work. In the bloodwork for both the initial heel prick and the follow-up screening test, plasma VLCFA concentrations are measured and C26:0 is used as the screening substrate. If the C26:0 concentration is still high in the second round of blood work, a referral to the genetics team is placed. The genetics team coordinates molecular testing to confirm the diagnosis and refers the families to endocrinology and neurology for treatment and management. If the patient has cerebral form, neurology coordinates bone marrow transplant for eligible participants. ¹⁵ Genetic counselors (GCs) act as a support system for the family, providing resources and referrals to help them navigate the medical system after receiving an abnormal result on the NBS. Additionally, PCPs also play an important role in coordinating patient care as they are the first step in the referral process. ¹⁶ Although PCPs are the first point of contact, studies show that many PCPs report a lack of confidence and are unprepared to manage a positive newborn screening result. ¹⁷ PCPs need to have sufficient knowledge and should be sensitive to parents’ emotions. Successful communication while delivering positive newborn screening results is important for establishing trust and enabling positive outcomes for the families.

Early diagnosis of X-ALD via NBS allows for monitoring and treatment. Males with X-ALD are seen by endocrinologists to get a baseline adrenocorticotropic hormone (ACTH) and cortisol level. They are also referred to a neurologist for evaluation and a brain MRI without contrast is recommended annually. ¹⁵ In terms of treatment, hematopoietic stem cell transplantation (HSCT) can stop cerebral demyelination. It is only effective if the patient is treated at an early stage.^7,13 NBS helps diagnose the cerebral form before it progresses past the point of effective treatment. In September of 2022, the FDA approved gene therapy for X-ALD boys with early progressive cerebral disease without a matched donor for HSCT, providing an alternative treatment method.

Understanding the families’ perspective regarding NBS for X-ALD will help healthcare providers improve patient care. Previous studies have been published with respect to the NBS process and families’ experiences of being diagnosed with other diseases such as Cystic Fibrosis and Pompe disease.^{18 -20} These studies shed light on the “patients in waiting” phase using the family systems genetic illness (FSGI) model, which explores how families understand their genetic risks and how genetic risk information influences the family as whole.^18,19 Different themes that arose in these studies were uncertainty, family dynamics, coping strategy, insurance concerns, and reproductive decisions. Despite experiencing fear and anxiety, all parents viewed NBS positively and had recommendations for healthcare providers (HCPs), including improving the referral process and reducing wait time and diagnostic delay. ²¹ Some parents felt the need for more accessible and parent-friendly information about NBS and the disease.^22,23

There is very limited literature on the NBS process for families being diagnosed with X-ALD. One study conducted in California looked at the impact of positive results of X-ALD in NBS on families. ²⁴ That study sheds light on the several psychosocial challenges faced by parents with children who screened positive for X-ALD on the NBS, exploring themes of stress, coping strategies, and family dynamics. Diverse coping strategies, including relying on faith, maintaining hope, and seeking information were exhibited by mothers. Many mothers strongly felt that screening for X-ALD should have been included in NBS. However, this study was unique to California’s screening process, and only included mothers. As more states in the US add X-ALD to their NBS panel, it is important to understand and improve the current model of the referral process.

The purpose of the present study is to explore the impact of a positive NBS result for X-ALD on families in other US states and include both parents/caregivers’ perspectives, focusing on the referral process. Families’ experiences with the referral process will yield informative data that may help us tailor the counseling and clinical care of these patients in the US.

Materials and Methods

English-speaking parents/caregivers of children identified with X-ALD via NBS in 1 of the 6 Southern states where NBS for X-ALD was being conducted at the time of data collection (Georgia, Tennessee, Florida, Kentucky, Texas, and North Carolina) were eligible to participate. This study was approved by the Emory University Institutional Review Board. Participants were recruited through NBS coordinators and GCs involved in the NBS and diagnostic process in these states. Recruitment emails indicated that the study was being conducted by a genetic counseling graduate student. No relationship was developed between the interviewer and the participants before study involvement. Because recollection of the events and perceptions may be different within couples, both parents/caregivers from each family were invited to participate. After informed consent was obtained, participants were asked to complete a short demographic survey on a HIPAA-compliant platform, REDCap. REDCap (Research Electronic Data Capture) is a secure, web-based software platform designed to support data capture for research studies, providing (1) an intuitive interface for validated data capture; (2) audit trails for tracking data manipulation and export procedures; (3) automated export procedures for seamless data downloads to common statistical packages; and (4) procedures for data integration and interoperability with external sources.^25,26

Following the survey, in-depth semi-structured interviews were conducted via Zoom with all study participants. Non-participants were not present during interviews. The interview guide was created by SI, a female genetic counseling graduate student, with input from NA (health psychologist, PhD), GG (genetic counselor, PhD MS), and AK (health scientist, PhD MS). The interview guide from the Schwan et al, ²⁴ study was also used as a reference. The general topics covered in the interview guide were questions about the referral process, interaction with healthcare providers, feedback for the process and the providers, and advice for other families. Interviews were recorded, transcribed verbatim, and de-identified by SI, who was trained in qualitative research methodology by NA as part of her graduate coursework. A thematic analysis was conducted following the general process of Braun and Clarke. ²⁷ Recurrent themes were analyzed using MAXQDA software. Two independent coders (SI and GG) analyzed the data using a codebook. The development of the codebook was iterative, including deductive codes based on prior literature on NBS for X-ALD and other disorders, and inductive codes arising from the data. Discrepancies in coding were noted and adjusted based on discussion and consensus. Inter-rater reliability was calculated using Cohen’s kappa (0.77). Interrater reliability was used to ensure consensus between coders and reduce bias in coding. Thick descriptions were generated for interview codes and thematic content analysis was conducted. ²⁸ All authors have studied and/or worked in the field of clinical genetics, and it is through this lens that data are interpreted. Data collection was stopped when no additional participants were forthcoming from the limited pool of potential participants. Data saturation was not assessed.

Results

Recruitment emails with the link to the survey were sent to the parents/caregivers of 22 children with X-ALD diagnosed via NBS in 6 states. At least 2 children moved to other states during the recruitment process. We received completed interest survey responses from 7 individuals, all of whom were interviewed between May 2022 and January 2023 regarding their perceptions of and experiences with the NBS screening and diagnosis process. Interviews lasted an average of 26 minutes (range: 16-35 minutes). This included 4 mothers and 3 fathers, representing 4 male children who screened positive for X-ALD. Only 1 child was symptomatic at the time of the interview. At the time of the interview, 1 child was 12 months, another child was 15 months, and 2 children were 18 months of age.

The primary themes that emerged during data analysis were lack of knowledge about NBS, parent’s reaction to initial result call out, interaction with PCP, interaction with other healthcare providers (including genetics, endocrinology, and neurology), overall opinion of NBS, and feedback to the healthcare providers. Each theme corresponds to a different part of the referral process. The referral process is divided into 3 stages – screening, diagnostic and treatment and management. Figure 1 represents the overview of the referral process for both Georgia and Kentucky (Table 1).

Figure 1.

Overview of the referral process.

Table 1.

Demographic Data.

Catergories	Demographic	Frequency
Gender	Male	3
	Female	4
Education	High School Diploma	2
	Associate degree	4
	4-year degree or more	1
Ethnicity	Hispanic/Latino	0
	Not Hispanic/Latino	7
Race	Asian	1
	Black or African American	3
	White	3
State of residence	Georgia	5
	Kentucky	2
Currently symptomatic child	Yes	1
	No	6
Health Insurance	Medicaid	2
	Private insurance	5

Lack of Knowledge about NBS

When the parents were asked if they were aware of what the heel prick test done on their newborn was for, 5 of them said they had no awareness and did not know what the bloodwork was looking for. Two of them said they had minimal awareness based on prior experience, but their respective partners were among the 5 who stated that they had no awareness:

To be honest, not really. With my first son, they just came in and stuck his heel, but nobody went into much depth. This test is for serious, lifelong diseases, but at the time, it was just, ‘Oh yeah, we’re going to test his blood.’ So, I thought they were testing his blood type and his blood count, and it never crossed my mind that they were testing for diseases because I don’t know anyone who has anything like that, and nobody had mentioned it to me.

Screening Process

Parent’s Reaction to Initial Result Call

Four of the participants said they received an initial phone call regarding the NBS screening result. Two of the four participants were from the same family; the mother heard the result and communicated it to the father. The 2 other participants who said they received a phone call had a perception of this part of the process that was different from what their partners said. Both of their partners said they heard the result in person. In total, 3 of them learned the results in person, and 3 of them said they learned the results from a healthcare provider, usually a pediatrician, and in 1 case, a genetic counselor. Four of them were unsure about who called, except that it was medical personnel.

Confusion and fear were the most common emotions among mothers. Two of the paternal perspectives included hurt, avoidance, and anger as the first emotional reaction. All of the parents were worried and lacked an understanding of the condition, which led to confusion. One father stated that he was in denial and refused to believe that his child had X-ALD. His perspective differed from that of his partner, who mentioned that their son was symptomatic and had adrenal insufficiency.

Interaction with Primary Care Providers

Some of the participants disliked the way the information was disclosed by the PCPs. Two mothers had negative feedback for the pediatrician. One mother said that the pediatrician did not believe her, and her obstetrician (OB) had never heard of this condition, so she had to research this information on her own. Another mother said that the pediatrician created a sense of panic and asked them to come into the office but never gave any actual information about X-ALD. One father said that it would be helpful to receive information about X-ALD when the initial results are given. They said they would like to have a better idea of the condition, and information found on the internet was very frightening:

It was a phone call and she was from the health department. I don’t know I really don’t feel like I was processing what was happening because. It just I don’t know I couldn’t like believe it because she was just like you know, “Your son was tested during his newborn screening, and he had a positive test for adrenoleukodystrophy.” And I remember, I had to write it down like three times because, first, I was like “What did she say like I didn’t get it”, and when I called them back. She said the same thing:” During your son’s newborn screening he tested positive for adrenoleukodystrophy, and they wanted to do a second test to be sure.” So now I’m calling my sister because she’s an RN but she’s in New York. She’s like “I never heard of that” so I’m like calling every health care person that I can and I’m like what is that, then I call it a pediatrician and the nurse there. She told me, but she told me so fast like it was still not I was like this cannot be true. It couldn’t.

One mother said that the pediatrician helped them stay calm and explained that it could be a false positive. Once the second bloodwork came in, he referred them to genetics:

And he didn’t worry me. He said just “Calm down. Let’s wait till we get another round of blood work”, he said, “whatever you do, don’t Google it and let’s just chill until we get the second round of blood work.”

After Initial Result Call Out

Five of the participants said that they went to see genetics after the initial result disclosure. The other 2 said that they went to see the pediatrician again after the second blood work, and then were referred to genetics.

Three of the parents said that they wished they had more information after the initial result was called out. They stated that they had to do their own research online before they met with a genetics provider.

Diagnostic Process

Interaction with Healthcare Providers

Genetics Providers

The time taken to meet with genetics after confirmatory bloodwork took anywhere between 1 and 4 weeks. One parent of the child who has adrenal insufficiency stated that genetics called them immediately and scheduled to see them within 5 days.

All parents said that the confirmatory test took about 4 to 6 weeks and the genetic counselor disclosed those results to them.

All 7 parents had positive feedback about the process with regards to meeting a genetic counselor and the geneticist. Six of them reported that it was the most informative appointment since the information was broken down and explained in a simple way:

The most helpful. I’ll say. The first trip to the counselor was the most helpful because it gave you the most information. They were there to help get started, like with the neuro and endocrinologist. They were there to really help get going, I mean I heard from them, the counselor I hadn’t. I don’t know if my wife still talks to them or not, or if we still got to see them but they was the best help to get started, and everything.

This interaction also reduced their anxiety. They said that the genetics appointment helped them get the right referrals and get set up with various providers in endocrinology and neurology. Everyone who tested positive received a referral to these specialties. One mother said that she discovered her carrier status through this, and that the GC helped arrange for carrier testing for other family members. Another mother stated that the GC was very supportive and always willing to answer emails and provide support. Two of the parents stated that because of COVID-19, only their partners were able to meet with the genetics providers. They felt less informed since they had to learn the information from their partner and did not have the opportunity to ask questions or be present for the appointment:

They’ve been awesome. I mean I’m glad they recommended who they did. I wouldn’t have wanted to go and pick my own doctors, because they know who’s best and what’s best.

Endocrinology and Neurology

Follow-up appointments for both endocrinology and neurology were scheduled every 3 to 6 months, with symptomatic individuals requiring more frequent appointments. One mother provided negative feedback for the endocrinologist and suggested that it would be more convenient to have bloodwork done before the appointment, allowing for a review of any abnormalities during the appointment. This was particularly important for her as she lived far away from the clinic and could not attend multiple appointments. She also recommended providing a laminated sheet or letter with information about X-ALD to take to the emergency room, since some rural healthcare centers may not be aware of the protocols for X-ALD. This letter should outline do’s and don’ts in case of abnormalities in the adrenocorticotropic hormone (ACTH) and cortisol levels. Additionally, she expressed difficulty in getting in touch with the endocrinologist’s team, leaving messages without receiving a response, and requesting better access to the care team, particularly in cases where laboratory results were abnormal. Overall, parents emphasized the importance of clear and accessible information and access to care teams for effective management of X-ALD:

And so that is a concern because I knew it wasn’t normal and they flagged it really high and it took me a while to get in touch with someone there because, obviously, like I said I’m a panic mom so worst case scenario went through my head and I didn’t have a clue what to do………So, they didn’t have the results to let me know I always check wherever whatever hospital we go to to get the blood work done. I log into their portal, so I can see it, because I know, sometimes it takes a while I don’t know for sure if they send it to Atlanta, so I like the check and make sure I have it and. So, they didn’t have it yet so I read and they finally called me back after like I called like six times and obviously they’re busy I mean it’s not their fault, you know they’re making rounds and doing. Seeing people. I’m just praying I wish there was like a 911 number, even though it wasn’t an emergency, thank goodness, but to me it was at the moment. Because I know I mean I’ll look for like I mean that is my kid about to like to pass out and then, what do I do because nobody in (my geographical area) knows anything about this.

Several of the parents interviewed (3 out of 7) reported that their care team has been helpful with coordinating and facilitating appointments, which has been especially important for families living far away. They have also received accommodation and prompt communication from their care teams. Additionally, 5 out of 7 parents reported that their insurance has covered all the costs for scans, labs, and appointments. One parent was unsure about the out-of-pocket costs as their child was on their partner’s insurance. However, his partner did report that their insurance did not cover CAT scans at every facility, but the provider wanted all scans and laboratory tests completed at the same facility due to logistic reasons. Overall, the parents in this study did not face significant issues with out-of-pocket costs or insurance coverage.

Support During the Entire Process

Two fathers did not have an established support system, while 2 mothers received emotional support from a physician assistant and OB after hours. Five parents relied on their family and friends for support. One mother found the GC to be supportive, always answering her emails and remaining in touch.

One mother, whose child had adrenal insufficiency, said that she was provided with a lot of resources after her appointment with the GC. She cited that the information sheets were helpful. She was referred to a support group as well but did not like going to support group meetings because it was very negative. She also mentioned that she would have preferred a referral to a therapist to help her cope with her situation. She felt like her appointments with healthcare providers were too brief and that she required someone outside of her family to provide additional support and help her navigate through this information in her postpartum period:

So, I used to attend the um Video meetings, but I had to stop because I’m gonna say like 85% of the time, there were a lot of parents that participated, but it was all just bad news like none of it was good news, and I just I couldn’t hear it. I couldn’t.

Overall Opinion on NBS

The NBS for X-ALD has elicited mixed reactions from parents. While most parents appreciated the knowledge it provides, some found it difficult to cope with the idea of their child having a potentially life-threatening condition. Many parents also expressed concerns about the medicalization of childhood and the impact on their ability to enjoy their child’s newborn phase. Additionally, some parents expressed discomfort with “toxic knowledge” and avoided thinking about it as their child appears healthy. Despite these challenges, many parents found the NBS to be helpful for early identification and management. One parent also said that she was grateful to NBS and that it was not available in her home country. She said it helped in identifying her carrier status and other family members who may be at risk (Tables 2 and 3).

Table 2.

Summary of Feedback for Screening Process.

Screening process
Positive feedback	Negative feedback
• One primary care provider calmed parent, explained possible false positive	• Confusion and fear were common among parents
• All got timely referral to genetics	• They disliked the way information was disclosed and needed more information after initial notification of results.

Table 3.

Summary of Feedback for Diagnostic Process.

Diagnostic process	Positive feedback	Negative feedback
Genetics	Most informative appointments, reduced anxiety, helped with referrals, arranged cascade testing, supportive and responsive GC	None mentioned
Endocrinology	Follow-up appointments scheduled regularly, coordinating appointments and facilitating care	Blood Work not done before appointment causing inconvenience, lack of accessibility to care team
Neurology	Follow-up appointments scheduled regularly, helpful care team for coordinating appointments and facilitating care	None mentioned
Insurance	Coverage for all costs for scans, labs, and appointments for most parents	Uncertainty about out-of-pocket costs for one parent

Discussion

This study sheds light on the X-ALD referral process in Georgia and Kentucky. The NBS process overall appeared to work efficiently. Everyone received timely and appropriate referrals throughout the process. This study is unique in that it included 3 paternal perspectives as well as maternal perspectives. It highlights the PCPs’ gaps in knowledge about NBS and X-ALD. It does bring up important recommendations for healthcare providers to further improve the process. Similar to other studies about parental experience with NBS, such as Pompe disease, SCID, and X-ALD, results show that parents experience a myriad of emotions.^19,29 In a study about PCPs’ role in NBS, PCPs agreed that they have an important role in this process. It also stated that parents valued the information learned from a trusted provider with whom they have a relationship. ³⁰ The results are also a reinforcing reminder of a need for newborn screening awareness in the general population

Although most parents did not like the initial result disclosure, 1 parent did state that their pediatrician helped them stay calm. This example highlights the importance of PCP’s role in communicating the initial result to anxious parents. There was emphasis on the need for better understanding of X-ALD during initial result disclosure. Parents felt that their PCPs were not fully aware of X-ALD. The ACMG ACT sheets are a resource that currently exist for PCPs. It can be used when one of their patients screens positive on NBS. Additionally, information and resources for conditions on the RUSP can be found on HRSA’s website (www.hrsa.gov) and babysfirsttest.org. PCPs should be made aware of these resources.

Parents stated that the genetics appointment was the most informative, and that the genetics providers gave a lot of support. This appointment reduced anxiety for most of the parents. Most of the parents looked for support within their families and healthcare providers. One mother said that she attended a support group to which she was referred, but that it was a very negative environment. She did not want to hear bad news from other families, and this was toxic knowledge for this participant.

Recommendations to Health Care Providers

The parents in this study believe that healthcare providers should provide parents with a brochure that outlines the purpose and importance of newborn screening, along with brief information about what tests will be conducted, how they will be conducted, and what it looks for before the heel prick. Both Georgia and Kentucky have a state-specific brochure with information about NBS available on their website. Parents might not recall this information since it could have been a very stressful period. It is unclear when and how these brochures were shared as it varies in different clinics. There are other educational initiatives, such as the Newborn Screening Family Education Program by Expecting Health which advocate towards increasing education about NBS for families. ³¹

Parents whose children screen positive for X-ALD should also be provided with information about X-ALD, including what it is, how it is diagnosed, and what treatment options are available. The information should be written in an easy-to-understand language and should be accompanied by fact sheets or pamphlets. We could also provide an information card and a medical identification bracelet to parents of males with X-ALD with information regarding possible adrenal insufficiency. While medical identification jewelry could be beneficial for patients with X-ALD, there are no current guidelines regarding its use. Based on studies of other chronic conditions, recommendations for medical identification jewelry by healthcare providers and use of such systems by patients are inconsistent.^{32 -34} The practices for prescribing medical identification jewelry can vary, but generally, it is the specialist (such as a geneticist or other medical expert) who understands the implications of the disorder and therefore prescribes it. Infants can typically wear medical alert jewelry on their wrists or ankles. The choice between the 2 often depends on the child’s comfort and the design of the bracelet. Clear standards for the prescription and use of medical alert jewelry among patients with X-ALD would be helpful (Table 4).

Table 4.

Recommendations for Healthcare Providers.

Summary of parents’ recommendation and feedback to healthcare providers
1.	State-specific brochure about newborn screening, given prior to heel prick
2.	Patient-friendly information and fact sheets about X-ALD to hand to parents at PCP’s office. Handouts with information about X-ALD for parents (and PCPs) are available through www.ALDAlliance.org
3.	Laminated protocol sheet or letter about X-ALD, with key points about do’s and don’ts in case of emergencies, which can be presented at the ER.
4.	Mandatory referrals to therapist for parents

One parent asked for a laminated protocol sheet or a letter from the endocrinologist that outlines what to do and what not to do in case of emergencies related to X-ALD. The sheet should be easy to follow when presented to other healthcare providers in the emergency room. For example, the emergency letter could include information such as how to treat adrenal insufficiency with glucocorticoid therapy because adrenal insufficiency if left untreated can be fatal. ⁴ Another recommendation was to refer parents to see a therapist to address any emotional or psychological issues that may arise as a result of their child’s diagnosis. The therapist should be experienced in working with families dealing with chronic illness and should be able to provide appropriate support and guidance.

Limitations

The survey was distributed to many families in the Southern US states which currently include X-ALD on their NBS panels. Although the goal was to recruit more participants from all 6 of these states, we only received responses from 2 states. Hence, our results may not be generalizable to other states. This study is limited by a small sample size, due to the rarity of the disorder and a low response rate. Only 4 out of 20 families responded (20%), with 7 people responding to the survey and participating in the interview. While the response rate was low, it is consistent with previous qualitative studies related to NBS.^35,36 A study on X-ALD conducted in Denmark also has a similar response rate. ³⁷ One other limitation of this study is the possibility of recall bias. This is because the parents were asked to reflect on a past period that was both stressful and emotional, which could have affected their perception of the experience. Moreover, the study found that there were differences in the maternal and paternal perspectives upon reflection, indicating that individual perspectives may influence recall bias. Maternal perspectives were generally more detailed. However, due to the small sample size, maternal and paternal perceptions could not be compared. We were also unable to compare the gap of knowledge between parents and previous children. Additionally, parents’ understanding of X-linked disorders was not assessed. Lastly, this study was only conducted with English-speaking participants.

Future Directions

Research recommendations include future studies with larger sample sizes, including more diverse perspectives. Studies should be carried out with more paternal perspectives and covering different states’ NBS processes. Future studies should also compare maternal and paternal perspectives and compare the knowledge gap between first time parents with previous children. Additionally, future research could assess PCPs’ knowledge and attitudes, and identify barriers to educational needs in genetics. Several NBS resources and educational materials which are geared towards families and healthcare providers exist, but there is still a lack of awareness and the barriers contributing to this must be assessed. A follow-up study can be conducted in the future about cascade testing, and experiences of female X-ALD carriers identified on NBS. For NBS diagnoses that were made during the pandemic, impact of COVID-19 on the process must also be assessed. Future research can also explore parents’ understanding of X-ALD and X-linked disorders. Parents’ retention of information and awareness a year later was not evaluated. Educational needs of parents might change based on that information and that can also be analyzed in future studies.

Conclusions

The study suggests ways to improve the experience of parents whose children are diagnosed with X-ALD through NBS. As more states add X-ALD to their NBS programs, it is important to understand the referral process and potential pitfalls to avoid. Improvements can be made by educating PCPs, creating more access to education materials, and providing mental health support to parents. These findings are particularly useful due to the lack of literature on NBS for X-ALD. These recommendations have implications for other states and countries considering adding X-ALD to their NBS programs in the future.