Introduction
Classic galactosemia (OMIM 230400) is an inherited disease of carbohydrate metabolism caused by a mutation in the Galactose-1-phosphate uridyltransferase (GALT) gene leading to a complete or near complete aberrance of GALT activity. Its incidence in the Netherlands is about 1:33,000 (Bosch et al.
2005), in the US 1 in about 47,000 live born children is affected (National Newborn Screening and Genetics Research Center
2002). Despite dietary treatment minimizing galactose intake, patients suffer from several long term effects of their disease, such as primary ovarian insufficiency, impaired mental abilities, decreased bone mass and suboptimal growth (Holton et al.
2001). It is becoming more and more clear that social problems may also be part of the spectrum of these complications.
Children with chronic diseases are confronted with their normal age-related development tasks, but must also learn to live with their chronic illness or disability. Performing developmental tasks is important for wellbeing and prevention of adjustment problems later in life (Garber
1984; Lewis and Miller
1990). A chronic condition in childhood could hamper the achievement of milestones, because the disease can lead to an increased dependence on parents and reduced participation in activities with peers. Cognitive development may be threatened, but also social development as a result of the disease or treatment. A recent publication demonstrated that the developmental trajectory of galactosemia patients is hampered. When compared with both a healthy reference group and a reference group of phenylketonuria patients they achieved fewer psychosocial developmental milestones such as participation in sports activities, going out and initiation of intimate relationships (Bosch et al.
2009).
Women with galactosemia suffer from subfertility, but no conclusive evidence on the male reproductive status in this disease exists. There is a striking lack of published fatherhood in these men, as to our knowledge only one father was ever reported (Panis et al.
2006). We do know that a few more galactosemic men have fathered a child (personal communication European Galactosemia Society), but there appears to be a discrepancy compared to the numerous women that conceived. Our recent study has shown that galactosemic men may face some fertility challenges, although infertility is rare (unpublished data). Young adults with chronic diseases face ongoing challenges to negotiate and obtain normative psychosocial developmental milestones and maintain adaptive functioning. Galactosemics appear to reach their social milestones at a slower pace than their peers, as was shown by Bosch and colleagues (
2009), but a limitation of this study was the small number of male patients that took part in the study: only three of the 15 patients were male.
To explore whether the percentage of male galactosemia patients that has achieved psychosocial developmental milestones was lower than the percentage among male peers from the general Dutch population, we have assessed their development with the Course of Life Questionnaire (CoLQ) (Stam et al.
2005).
Discussion
This study shows a significant delay in both psychosexual development as well as social development in young adult men with galactosemia. These findings are comparable to those seen in the whole group of galactosemia patients (Bosch et al.
2009). The delay might in part explain the low number of galactosemic fathers.
These findings indicate that it is important to encourage children (boys) with galactosemia to make friends and to participate in peer activities. Peer relationships are important for social development and self-esteem, especially in adolescents. Adolescents with chronic illnesses may become marginalised by peers, rejected for being different at a time when body image and identity so largely depend on conformity (DiNapoli and Murphy
2002). From previous research we know that social development seemed to be related to psychosexual development (Stam et al.
2005), so that friendships in youth are probably important for later sexual relationships.
This study has some limitations. We included patients in two different countries, whereas the reference group is from the Netherlands only. The comparison between the Dutch and the American patients, however, did not show any significant difference (at p < 0.01), so that comparison with the Dutch reference group seemed justified. Another limitation is the small sample size. As a result, we decided to include patients up to 35 years while the reference group was aged up to 30 years. A strength of the study is that, compared to the total number of known Dutch galactosemia patients, and the number of American patients asked to participate, a relatively large number of patients decided to enrol.
Future research is necessary to confirm the results of the present, exploratory study, and to describe the relation between developmental achievements and later adjustment. The underlying reason behind the developmental delay in galactosemic men perhaps could be found in social skills. Generally, galactosemia patients are described as more timid than their peers. Furthermore, cognitive dysfunction, which is another complication of classic galactosemia, can interfere with normal social and psychosexual development as was described for childhood cancer survivors (Gurney et al.
2009). This might make it more difficult for galactosemia patients to develop a healthy relationship and start a family. The known problems with language development might be another contributor to this problem.
Perhaps early intervention, such as the speech therapy and social competence training (Last et al.
2007) that many young galactosemia patients currently receive, could lead to a better outcome for future generations. Furthermore, currently therapeutic strategies aimed at preventing and confining long term complications of classic galactosemia are being developed. For physicians it is very important to be aware of a possible delay in galactosemia patients, as it could be important to address problems that may arise during consultations. Paying attention to quality of life during consultations using patient-reported outcomes could be a valuable addition in clinical care (Engelen et al.
2010 (Epub ahead of print)).
In conclusion, men with classic galactosemia have severe delays in social and psychosexual development, as has been shown in a group of galactosemia patients of both sexes before. We strongly support routine screening for social and psycho-sexual development so that intervention is possible at an early age.