Age-dependent penetrance among females with X-linked adrenoleukodystrophy

Adrenoleukodystrophy in Norway: High Rate of De Novo Mutations and Age-Dependent Penetrance

“…However, increased experience with and systematic studies of X-ALD populations have, during the last decades, changed our view of X-ALD on three important areas: Firstly, it is now increasingly recognized that AMN may be the basic and most frequent phenotype of X-ALD [4]. Secondly, recent research [8,9,35] has established that most or all females with X-ALD will develop some degree of neurological involvement, with an age-dependent penetrance. Thirdly, evidence is accumulating that CER may develop beyond childhood, even in full grown males with AMN [35][36][37], possibly triggered by external factors such as head trauma [38].…”

“…USA [76], Japan [77] and South Brazil [78] (see Table 2). Our Paper 1 [35] is the latest offshoot of this expanding scope of X-ALD epidemiology, using the widest…”

“…The c.1415delAG mutation is the most common, having been identified in about 10 % of X-ALD kindreds [33] (including one of the 23 Norwegian kindreds with an established mutation [35]). However, a general observation is that each family has its own, "private" mutation; each population studied has its own mix of mutations [35,97,98]. This makes mutational analysis in a subject dependent on whether the family mutation has been identified or not.…”

“…HCST has also been offered to adult patients developing CER at French and German centers [4,88]. With emerging evidence that the lifetime risk of CER is high in males [35][36][37], thorough data on efficacy, tolerability and long-term survival of HCST performed in adult males need to be obtained.…”

“…Females diagnosed early in life must now cope with a more somber prospect of the disease than previously envisioned, as recent research [8,9,35] indicates that the vast majority will develop some degree of neurological involvement during life.…”