Fabry patients' experiences with the timing of diagnosis relevant for the discussion on newborn screening.

This study aimed to explore Fabry disease (FD) patients' experiences with the timing of their diagnosis and identify important patient-oriented themes relevant to discussions about the need for newborn screening (NBS) for this disorder. Thirty FD patients (13 males) were included in a qualitative study involving semi-structured interviews. The interviews were audiorecorded and transcribed, and the transcripts were analyzed to identify themes that captured the patients' experiences. The interview analysis revealed six relevant themes. One of these was the impact of a delayed diagnosis on severely affected patients, who often felt misunderstood and were frequently misdiagnosed. In contrast, some patients mentioned the drawbacks of presymptomatic diagnosis, which was associated with labeling and medicalization. In addition, the ability to anticipate future FD-related problems was considered both an advantage and a disadvantage of early diagnosis. Still, patients reported that they felt that an early FD diagnosis could prevent disease progression through the timely initiation of treatment. This study identified several relevant themes that reflect both the phenotypic heterogeneity of the disease and the substantial differences between patients' experiences with and without FD symptoms before diagnosis and among the patients in each group. These results add considerable nuances to the discussion about NBS programs for FD and should be incorporated into the debate.

Long term enzyme replacement therapy for Fabry disease: effectiveness on kidney, heart and brain.

BACKGROUND: Fabry disease is an X-linked lysosomal storage disorder caused by α-galactosidase A deficiency leading to renal, cardiac, cerebrovascular disease and premature death. Treatment with α-galactosidase A (enzyme replacement therapy, ERT) stabilises disease in some patients, but long term effectiveness is unclear. METHODS: Renal, cardiac, and cerebral outcomes were prospectively studied in males and females with Fabry disease treated with ERT. Additionally, the occurrence of major cardiac events, stroke, end-stage renal disease and death was compared to a natural history (NH) cohort meeting treatment criteria. RESULTS: Of 75 patients on ERT (median treatment duration 5.2 years, range 0.05-11.0), prospective follow-up was available for 57 adult patients (30 males) and 6 adolescents. Renal function declined in males (-3.4 ml/min/1.73 m2 per year, SE 0.2; p < 0.001) despite ERT, but followed the normal course in females (-0.8 ml/min/1.73 m2 per year, SE 0.3; p = 0.001). Cardiac mass increased during ERT in males (+ 1.2 gram/m2.7, SE 0.3; p < 0.001), but remained stable in females (-0.3 gram/m2.7 per year, SE 0.4; p = 0.52). ERT did not prevent the occurrence of cerebral white matter lesions. Comparison of ERT treated to untreated patients revealed that the odds to develop a first complication increased with age (OR 1.05 (95% CI: 1.0-1.1) per year, p = 0.012). For development of a first or second complication the odds declined with longer treatment duration (OR 0.81 (95% CI: 0.68-0.96) per year of ERT, p = 0.015;OR 0.52 (0.31-0.88), p = 0.014 respectively). CONCLUSIONS: Long term ERT does not prevent disease progression, but the risk of developing a first or second complication declines with increasing treatment duration. ERT in advanced Fabry disease seems of doubtful benefit.

Experiences of parents and patients with the timing of Mucopolysaccharidosis type I (MPS I) diagnoses and its relevance to the ethical debate on newborn screening.

INTRODUCTION: Newborn screening (NBS) techniques have been developed for several lysosomal storage disorders (LSDs), including Mucopolysaccharidosis type I (MPS I). MPS I is an LSD with a wide phenotypic spectrum that ranges from the severe Hurler phenotype to the attenuated Scheie phenotype. To improve the ethical discussion about NBS for MPS I, we performed an interview study to explore the experiences of MPS I patients and their parents with the timings of their diagnoses. METHODS: We used a qualitative research approach consisting of 17 interviews with the parents of patients with all MPS I phenotypes and with patients with attenuated forms of MPS I. The interviews were audio-recorded, transcribed and subsequently analyzed to identify the main themes identified by the participants. RESULTS: Five important themes, focusing on the experienced disadvantages of delayed diagnosis and the advantages and disadvantages of a hypothetical earlier diagnosis, were identified in our group of participants: 1) delayed diagnosis causing parental frustration, 2) delayed diagnosis causing patient frustration, 3) early diagnosis enabling reproductive decision-making, 4) early diagnosis enabling focusing on the diagnosis, and 5) early diagnosis enabling timely initiation of treatment. There was a remarkable similarity in the experiences with timing of diagnosis between parents of patients with the severe and the attenuated forms. CONCLUSION: This was the first study to explore the personal experiences of MPS I patients and their parents with diagnostic timing. Our study identified five important themes that are highly relevant to the ethical discussion on expanding NBS programs for MPS I.

Prevalence of symptoms in female Fabry disease patients: a case-control survey.

BACKGROUND: Fabry disease (FD) is an X-linked lysosomal storage disorder, caused by a deficiency of α-galactosidase A. Several studies demonstrated that heterozygotes have symptoms such as acroparesthesia, abdominal pain and chronic fatigue. However, as these symptoms are aspecific and relatively common in the general population, it is important to compare the prevalence of these symptoms with an appropriate control group. The aim of this study was to explore the prevalence of signs and symptoms in FD females in comparison to a control group. METHODS: FD females and age-matched controls were approached to complete a questionnaire. This questionnaire was developed by the Dutch Fabry patient organisation (Fabry Support en Informatie Groep Nederland, FSIGN) with input from Fabry expert-physicians from the AMC. We compared the prevalence symptoms using Pearson's chi-square test. Bonferroni correction was used to correct for multiple comparisons. RESULTS: A total of 63 heterozygotes and 52 controls completed the questionnaire. Many symptoms were also common in controls. Yet, fatigue, palpitations, pains in hands and feet, joint pain, dizziness, loss of libido and proteinuria during pregnancy were more common in Fabry females (all p < 0.001). CONCLUSION: In addition to acroparesthesia - fatigue, palpitations, dizziness, proteinuria during pregnancy, libido loss and joint pain are more prevalent in FD females as compared to a control group. Although, these symptoms are present in a significant proportion of normal controls they deserve further attention by treating physicians to better understand their significance, treatment and relationship with FD.

Impact of growing up with Fabry disease on achievement of psychosocial milestones and quality of life.

Little is known on the impact of growing up with Fabry disease (FD) on psychosocial development. Children with FD may suffer from severe recurrent pains in hands and feet, gastro-intestinal symptoms and heat intolerance. These symptoms may influence quality of life and may interfere with a normal psychosocial development. It is important to evaluate psychosocial outcomes of patients with FD into adulthood to be able to optimize support of children with FD. The current cross-sectional questionnaire study investigated psychosocial development and quality of life of 28 young adults with FD, aged 18-35 years (9 males, 19 females), using the Course of Life questionnaire and the Short Form-36 questionnaire for quality of life. The results were compared with an age-matched normative population. We found significant differences in the achievement of milestones in social development of male Fabry patients. The milestones that were affected were 'going out to bars' and 'participation in sports activities'. Other than that FD patients appear to be able to achieve a rather normal psychosocial development until adulthood. Quality of life was decreased in Fabry males in the domains of physical functioning and bodily pain and of general health perception in females.

'Doctor Google' ending the diagnostic odyssey in lysosomal storage disorders: parents using internet search engines as an efficient diagnostic strategy in rare diseases.

The expansion of the internet has resulted in widespread availability of medical information for both patients and physicians. People increasingly spend time on the internet searching for an explanation, diagnosis or treatment for their symptoms. Regarding rare diseases, the use of the internet may be an important tool in the diagnostic process. The authors present two cases in which concerned parents made a correct diagnosis of a lysosomal storage disorder in their child by searching the internet after a long doctor's delay. These cases illustrate the utility of publicly available internet search engines in diagnosing rare disorders and in addition illustrate the lengthy diagnostic odyssey which is common in these disorders.