Metabolic and Nutritional Aspects in Paediatric Patients with Klinefelter Syndrome: A Narrative Review.

Klinefelter syndrome (KS) is the most common sex chromosomal aneuploidy in males.

• KS is characterized by the presence of one or more supernumerary X chromosomes, with the 47,XXY karyotype being the most frequent.
• Prevalence is estimated at approximately 1 in 500–1000 male births.
• KS is frequently underdiagnosed, with many cases identified only in adulthood.
• The paediatric population with KS remains understudied compared to adults.

Patients with Klinefelter syndrome have greater mortality and morbidity compared to the general population due to cardiovascular diseases and endocrine metabolism disorders.

• Increased risk is attributed both to hypogonadism and to the syndrome itself.
• Cardiovascular disease risk is elevated in KS patients independent of testosterone deficiency.
• Endocrine disorders including diabetes mellitus, metabolic syndrome, and dyslipidemia are more prevalent in KS.
• Early primary prevention strategies are considered crucial to managing long-term outcomes.

Boys with Klinefelter syndrome exhibit a distinct body composition phenotype characterized by increased fat mass and reduced lean mass.

• Altered body composition in KS children precedes the onset of overt hypogonadism, suggesting the role of the supernumerary X chromosome itself.
• Increased adiposity, particularly visceral fat, contributes to metabolic risk.
• Reduced muscle mass is associated with lower physical activity levels and fatigue commonly reported in KS patients.
• Body composition abnormalities are present even in prepubertal KS boys.

Children with Klinefelter syndrome show an increased prevalence of metabolic syndrome components including dyslipidemia, insulin resistance, and hypertension.

• Insulin resistance and impaired glucose metabolism have been documented in paediatric KS patients.
• Dyslipidemia, including elevated triglycerides and reduced HDL cholesterol, is reported in children with KS.
• Hypertension risk is increased in KS, contributing to overall cardiovascular risk.
• These metabolic alterations are observed before the initiation of testosterone replacement therapy, implicating non-hormonal pathogenic mechanisms.

Testosterone replacement therapy (TRT) in Klinefelter syndrome has beneficial effects on metabolic parameters, body composition, and quality of life.

• TRT helps reduce fat mass and increase lean body mass in KS patients.
• Hormonal replacement therapy is considered crucial to reducing cardiovascular and metabolic risk.
• Timing of TRT initiation, particularly during puberty, may influence long-term metabolic outcomes.
• Despite benefits, TRT does not fully normalize metabolic risk in KS, supporting the role of the syndrome itself beyond hypogonadism.

Nutritional aspects, including dietary habits and micronutrient status, are relevant to the metabolic risk profile of paediatric KS patients.

• Only a few studies have specifically focused on nutritional assessment in the paediatric KS population.
• Dietary interventions targeting obesity prevention and metabolic risk reduction are considered important in KS management.
• Micronutrient deficiencies may be present in KS patients, though data in children are limited.
• Lifestyle modifications including nutrition and physical activity are emphasized as part of early primary prevention strategies.

Bone health is compromised in children with Klinefelter syndrome, with reduced bone mineral density reported.

• Low bone mineral density (BMD) is a recognized complication of KS, partly attributed to hypogonadism and testosterone deficiency.
• Reduced BMD increases the risk of osteoporosis and fractures in adulthood.
• Bone health abnormalities may be present in paediatric KS patients prior to puberty.
• Adequate calcium and vitamin D intake, along with TRT, are important for bone health optimization in KS.

There is a paucity of data specifically addressing metabolic and nutritional aspects of Klinefelter syndrome in the paediatric population.

• Most available studies on KS metabolism and nutrition have been conducted in adult populations.
• The authors highlight the need for longitudinal studies focused on children and adolescents with KS.
• Early identification and intervention in paediatric KS patients are emphasized to prevent long-term complications.
• A multidisciplinary approach involving endocrinologists, nutritionists, and other specialists is recommended for paediatric KS management.