The manifestation of symptoms, impacts of the disease, management and treatment considerations for women with the Fabry gene vary considerably. While males have only one X chromosome in each cell, females have two X chromosomes in every cell and subsequently, two copies of the gene responsible for the production of the enzyme alpha-galactosidase A. Females who have been historically, but no longer, considered only "carriers" for Fabry disease have one normal copy and one altered copy of the gene. The resulting level of enzyme activity may vary greatly among females, and therefore some females may be significantly affected while others show no symptoms.
Research indicates many more females suffer cellular damage from Fabry disease than previously thought. If fact, recent studies reveal that asymptomatic female carriers of Fabry disease are the exception, not the rule (Laney, Fernhoff 2008; Wang et al. 2007; Whybra et al. 2001). Fabry disease should no longer be considered a typical X-linked recessive dosorder as previously thought. Non-random or skewed, X-chromosome inactivation is thought to be one of the primary causes for this phenomenon but may not entirely explain the large numbers of affected females. See
random X inactivation.
Females must be closely monitored by their physicians. Regular monitoring is essential in order to detect damage or symptoms and to determine appropriate management.
Just as with men, however, ignoring symptoms because they seem bearable or assuming an individual's health is good because there seems to be no significant signs of Fabry disease, may be unwise. The progression of many of the severe symptoms of Fabry disease such as heart disease, kidney disease and strokes may not be realized without proper periodic clinical monitoring regardless of how an individual may feel. And, many of the non-life-threatening but potentially life-altering symptoms such as pain and gastrointestinal issues may be indications of Fabry disease progression which may require more frequent monitoring and possibly treatment.
The statements below are extracted from the Genetics in Medicine article (September 2006, Vol - 8 - No 9) entitled "Fabry disease: Guidelines for the evaluation and management of multi-system involvement". (link below - subscription required):
"Disease presentation in female heterozygotes may be as severe as in males although women may also remain asymptomatic."
"In contrast [to males], a much lower proportion of females suffer progressive renal dysfunction to the point of end-stage renal disease or transplantation."
"The heart is frequently involved in the various phenotypic variants of Fabry disease, including women with clinical disease and males with the cardiac variant."
"Onset of CNS [central nervous system] symptoms has been shown to occur earlier in males (age 34) than in females (age 40)."
"Chronic cough is a common complaint in men as well as women."
"Exercise intolerance in Fabry disease is typically attributed to hypohidrosis, pulmonary disease, or cardiomyopathy, but can begin in early childhood and is not uncommon in female patients."
"A recent study revealed a decrease in diastolic blood pressure equal to or > than 10mmHg during exercise testing in approximately half of the patients studied, with the largest declines occurring in females."
"Angiokeratomas ... are one of the earliest clinical signs and may be seen in both genders."
"Among female carriers, frequencies of occurrence of angiokeratomas up to 35% have been reported."
"The pattern of streaks [corneal opacities] is often most predominant in heterozygous females."
"The mean age of onset of disease complications in females and the age of death appear to be later than in males. Affected females may display all of the classical symptoms but previously unsuspected Fabry disease has also been found in women with isolated organ involvement. The frequency of hypertrophic cardiomyopathy and cerebrovascular accidents (strokes, transient ischemic attacks) may be increased in females over the age of 40."
Additional information about females affected by Fabry disease can be found in the recent journal article: below entitled: "Diagnosis of Fabry Disease via Analysis of Family History"..
