Fabry Disease in Pregnancy: A Case Report

Abstract

Introduction: Fabry disease (FD) is an X-linked lysosomal deposit disorder caused by a deficiency in the enzyme lysosomal α-galactosidase A (α GAL-A) and the accumulation of globotriaosylceramide (Gb3) in the nervous, cardiovascular, and renal systems. Initially thought to be predominantly male, it has evolved to include heterozygous women with a diverse range of clinical symptoms. FD can pose health risks to the mother and her offspring during pregnancy, childbirth, and the neonatal period. The disease begins during the fetal stage of development, with most affected children remaining asymptomatic for the first few years. Progression of FD is associated with decreased renal function and proteinuria, and adults usually die prematurely due to organ failure. FD affects 1 in every 117,000 newborns, with an estimated prevalence between 1:40,000 and 1:117,000.

Clinical case: A 17-year-old Mexican female patient was diagnosed with Fabry's disease eight years ago, with no history of treatment. She had no history of drug or food allergies, no surgical history, and a history of renal failure due to Fabry's disease. The patient was hospitalized due to a 37.5-week term pregnancy, without labor, and no history of hypertensive disease in the pregnancy, threat of abortion, or preterm delivery. During hospital admission, medical evaluations were conducted by ophthalmology, cardiology, internal medicine, and psychology. The patient had no impairment of visual acuity, but had vascular tortuosity and glucosphingolipid deposits in the corneal stroma. The cardiac cavities were normal, and no significant valve diseases were found. The patient was asymptomatic at the time of admission and had a single delivery of a live newborn without apparent complications. Genetic monitoring was decided for an early diagnosis and timely pharmacological therapy to decrease comorbidities typical of Fabry's disease.

 Discussion: Fabry disease (FD) is a rare chromosome-linked X-chromosomal disorder that alters lysosomal storage functions, caused primarily by mutations in the GLA gene encoding α-galactosidase A (α-GAL-A). It begins with cellular dysfunction and progresses over several years, eventually causing functional organ deterioration. Patients with FD experience multiple organ failure, with the kidneys, heart, and brain being the most susceptible organs. Initially predominantly male, women with FD have a diverse range of clinical symptoms and experience a level of clinical severity often equivalent to that observed in men. The onset of early symptoms and complications in adulthood tends to occur later in women. Pregnancies among women with FD revealed a higher prevalence of pregnancy-specific complications compared to the general population, but no life-threatening consequences were documented. Specific concerns related to women with FD during pregnancy involve the potential impact of microvascular disease, which can increase the risk of coagulation and exacerbate kidney function.

The burden of disease in pregnant women with FD is not well understood due to its low prevalence. Prenatal diagnosis of FD is usually made late due to the lack of initial specificity of the presentation symptoms. The first laboratory test is usually an assessment of GLA activity, with genetic analysis of mutations in the GLA gene being the gold standard. Prenatal diagnosis of FD can be achieved by demonstrating a karyotype XY and deficient α-GAL-A activity in chorionic villi or cultured amniocytes, or by prenatal molecular analysis if the fetus is female. The American Society of Genetic Counselors recommends fetal sex determination as the first diagnostic step in genetic counseling for families with a history of fetal deficiency (FD). Optimal management of pregnant patients with FD requires a dedicated multidisciplinary team. Enzymatic replacement therapy (ERT) is the cornerstone of comprehensive treatment, and early initiation is crucial for long-term benefits. The use of agalsidase alpha in pregnant women has been effective, but its efficacy may vary due to factors like age of onset and disease burden. Regular monitoring is essential for detecting early signs of disease progression.

Conclusion: Fabry disease affects women's quality of life and health system barriers, leading to delayed diagnosis and treatment. Despite its rarity and gender bias, individualized management during pregnancy is crucial. Enzyme replacement therapy should be evaluated in a multidisciplinary team. Family screening is essential for early diagnosis and management. Documenting treatments and results is crucial for future therapeutic decisions.