Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism

Poloni, Soraia; Leistner-Segal, Sandra; Bandeira, Isabel Cristina; D’Almeida, Vânia; Souza, Carolina Fischinger Moura de; Spritzer, Poli Mara; Castro, Kamila; Tonon, Tássia; Nalin, Tatiéle; Imbard, Apolline; Blom, Henk J.; Schwartz, Ida Vanessa Döederlein

doi:10.1016/j.gene.2014.05.015

Cited by 15 publications

(13 citation statements)

References 23 publications

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“…Another phenotypic trait commonly shared by HCU patients is a thin build, low body fat content, and lower body mass index (BMI) than the age‐matched general population (Brenton, Dow, James, Hay, & Wayne‐Davies, ; Gibson, Carson, & Neill, ; Mudd et al., ; Poloni et al., ). Here we show that the KO and the I278T but not the HO mouse model replicate the body composition typical for HCU patients by overall lower mass and markedly decreased body fat content.…”

Section: Discussionmentioning

confidence: 99%

Enzyme replacement therapy prevents loss of bone and fat mass in murine homocystinuria

Majtán

Park

Bublil³

et al. 2017

Human Mutation

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Skeletal and connective tissue defects are the most striking symptoms in patients suffering from classical homocystinuria (HCU). Here, we determined body composition and bone mass in three mouse models of HCU and assessed whether a long-term administration of enzyme replacement therapy (ERT) corrected the phenotype. The mouse models of HCU were analyzed using dual-energy X-ray absorptiometry and the data were complemented by plasma biochemical profiles. Both the mouse model lacking CBS (KO) and the one expressing human CBS mutant transgene on a mouse CBS null background (I278T) showed marked bone loss and decreased weight mostly due to a lower fat content compared with negative controls. In contrast, the HO mouse expressing the human CBS WT transgene on a mouse CBS null background showed no such phenotype despite similar plasma biochemical profile to the KO and I278T mice. More importantly, administration of ERT rescued bone mass and changes in body composition in the KO mice treated since birth and reversed bone loss and improved fat content in the I278T mice injected after the development of clinical symptoms. Our study suggests that ERT for HCU may represent an effective way of preventing the skeletal problems in patients without a restricted dietary regime.

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Section: Discussionmentioning

confidence: 99%

Enzyme replacement therapy prevents loss of bone and fat mass in murine homocystinuria

Majtán

Park

Bublil³

et al. 2017

Human Mutation

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“…83–88 Reduced fat mass and lower BMI are common in patients with classical homocystinuria, and in addition cysteine concentrations showed a positive correlation with BMI, while homocysteine and methionine levels were negatively correlated with BMI. 86,89 …”

Section: Discussionmentioning

confidence: 99%

Adolescent BMI at Northern Israel

et al. 2016

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The increasing prevalence of abnormal body mass index (BMI), mainly obesity, is becoming a significant public health problem. This cross-sectional study aimed to provide a comprehensive view of secular trends of BMI, and the associated socio-demographic variables and comorbidities among adolescents with abnormal BMI. Individuals of the study population were born mainly between 1970 and 1993, and were examined at 16 to 19 years of age during the years 1987 to 2010, at 1 conscription center in the northern district of Israel.The study population included 113,694 adolescents. Univariate and multivariable logistic regression models were used to investigate the associations between BMI categories, socio-demographic variables, and medical conditions.A downward trend in the prevalence of normal BMI among both male and female adolescents was obtained, while trends of overweight and obesity (in both genders) and underweight (only among females) rose. Socio-demographic variables such as religion, education, family-related parameters, residential environment, country of birth, and origin were all associated with different risks for abnormal BMI. Obesity was associated with higher risk for hyperlipidemia, endocrine disorders (only in males), knee disorders, and hypertension type I + II (in both genders). Overweight was associated with knee disorders (only in females). Underweight, exclusively in males, was associated with increased risk for endocrine disorders, proteinuria, and cardiac disorders. Hierarchical clustering analysis revealed the intricate relations between gender, BMI, and medical signatures. It brought to light novel clusters of diseases that were abundant among populations having above-normal BMI or underweight males. Furthermore, above-normal BMI was associated with a lower rate of cardiac anomalies and scoliosis/kyphosis, whereas being underweight was associated with a lower risk for hypertension and flat foot.This study provides a reliable and in-depth view of secular trends in height, weight, and BMI of male and female adolescents. It supports previous associations between abnormal BMI and demographic variables and comorbidities, while uncovering novel associations, mainly regarding medical signatures of each gender–BMI group. This might lead to better monitoring, early detection, prevention, and treatment of various conditions associated to abnormal BMI categories and gender groups.

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“…The appearance of untreated CBS deficient patients often resembles that of individuals with Marfan syndrome, characterized by arachnodactyly, scoliosis, low BMI, and reduced fat [47–49]. Adult patients with CBS deficiency show radiologic evidence of osteoporosis or decreased bone mineral density [50].…”

Section: Skeletal Fat Mass and Hair Abnormalitiesmentioning

confidence: 99%

Cystathionine β-synthase deficiency: Of mice and men

Kruger

2017

Molecular Genetics and Metabolism

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Cystathionine β-synthase (CBS) deficiency (Online Mendelian Inheritance in Man [OMIM] 236200) is an autosomal recessive disorder that is caused by mutations in the CBS gene. It is the most common inborn error of sulfur metabolism and is the cause of classical homocystinuria, a condition characterized by very high levels of plasma total homocysteine and methionine. Although recognized as an inborn error of metabolism over 60 years ago, these is still much we do not understand related to how this specific metabolic defect gives rise to its distinct phenotypes. To try and answer these questions, several groups have developed mouse models on CBS deficiency. In this article, we will review various mouse models of CBS deficiency and discuss how these mouse models compare to human CBS deficient patients.

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Body composition in patients with classical homocystinuria: body mass relates to homocysteine and choline metabolism

Abstract: These results suggest that reduced fat mass is common in patients with classical homocystinuria, and that alterations in homocysteine and choline pathways affect body mass and lipid metabolism.

Cited by 15 publications

References 23 publications

Enzyme replacement therapy prevents loss of bone and fat mass in murine homocystinuria

Enzyme replacement therapy prevents loss of bone and fat mass in murine homocystinuria

Adolescent BMI at Northern Israel

Cystathionine β-synthase deficiency: Of mice and men

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