Journal of Obesity and Metabolism
Open Access

Galactosemia; Genetic disorder; Galactose; Enzyme deficiency; Metabolism; Milk; Dairy products; Infant

Introduction

Galactosemia is a rare genetic disorder characterized by the body’s inability to properly metabolize galactose, a sugar found in milk and dairy products [1]. It is caused by a deficiency or absence of certain enzymes that are essential for breaking down galactose into glucose, which can be used for energy. As a result, galactose builds up in the body, leading to various complications if left untreated.

This disorder is typically diagnosed shortly after birth through newborn screening programs, which allow for early intervention and management. Infants with galactosemia may exhibit symptoms such as poor feeding, vomiting, diarrhea, jaundice, and failure to thrive. If the condition goes undiagnosed and untreated, it can lead to severe complications including liver damage, kidney problems, cataracts, intellectual disability, and developmental delays.

The mainstay of treatment for galactosemia is a strict galactose-free diet. This involves eliminating all sources of galactose and lactose from the individual’s diet, which includes avoiding milk, dairy products, and certain by-products that may contain these sugars. Infants with galactosemia are usually fed with specialized formulas that do not contain galactose or lactose. Adherence to this diet throughout life is necessary to prevent the development of complications and ensure optimal health.

Genetic counseling is often recommended for families with a history of galactosemia, as the condition follows an autosomal recessive inheritance pattern. This means that both parents must carry and pass on a mutated gene for their child to be affected. By understanding the genetics of galactosemia, families can make informed decisions and receive appropriate support.

While galactosemia cannot be cured, early diagnosis and strict dietary management enable individuals with the condition to lead relatively normal lives [2]. Regular monitoring and medical follow-up are essential to assess the effectiveness of the diet, detect any potential complications, and provide necessary support and interventions. Ongoing research continues to improve our understanding of galactosemia and explore potential treatments to enhance the quality of life for affected individuals.

In particular, previous studies have shown that people of European, African, and Asian ancestry, among others, have CG/CVG, and disease prevalence varies greatly by ancestral group. For instance, CG affects approximately 1/430 Romani births in Ireland. The percentage of non- Romani people in Ireland is about 1/34,000. The prevalence in the Netherlands is approximately 1/52,800. The prevalence rate is estimated to be 1/14,500 in Africa. A prevalence rate of close to 1/50,000 screened births has been reported in the United States (USA). Among Asian populations, the prevalence of CG/CVG has been found to be the lowest.

The current study had as one of its objectives the description and comprehension of any variation in the prevalence of CG/CVG among people of differing ancestry living in a nation of racially and ethnically diverse people with almost universal NBS for galactosemia: the States of America First, we combined publicly available allele frequency data stratified by ancestry with birth certificate data listing the racial and ethnic composition of the US newborn population to predict the expected frequency of CG/CVG [3]. Then, we compared the predicted rates of CG/CVG occurrence with the rates that were observed in the available NBS data for the same time period to see if our calculations were accurate.

Methods and Materials

Four pre-pubertal female patients with classic galactosemia underwent ovarian tissue cryopreservation (OTC) via laparoscopic unilateral oophorectomy in accordance with a protocol that was approved by the Institutional Review Board in order to preserve their fertility. Informed consent was given by each patient along with their parent or guardian. Pathology was tasked with performing H&E staining and histologic analysis on a small portion of this tissue. Using the HALO LinkTM Image Analysis Platform, the cortex area and total follicle density of each slide were determined [4]. A distance of one millimeter along the edge of the tissue sample was used to measure the cortex area. By comparing the total number of follicles per cortex area (follicles/mm2), the total follicle density was determined. In the coming months, additional classification of follicle subtypes will be reported.

The methods and materials used in the management and treatment of galactosemia primarily revolve around dietary modifications, medical monitoring, and genetic counseling. Here are the key components:

Diagnosis: Galactosemia is often diagnosed through newborn screening programs, which involve collecting a small blood sample from newborns to test for the presence of galactose and related metabolites [5]. The screening typically uses techniques such as enzymatic assays or tandem mass spectrometry.

Dietary modifications: Galactose-free diet: The cornerstone of galactosemia management is a strict galactose-free diet. This involves eliminating all sources of galactose and lactose from the individual’s diet. Foods such as milk, dairy products, and certain by-products need to be avoided.

Specialized formulas: Infants with galactosemia are typically fed with specialized formulas that are free from galactose and lactose [6]. These formulas provide necessary nutrients while ensuring the exclusion of galactose-containing ingredients.

Medical Monitoring: Regular blood tests: Individuals with galactosemia undergo periodic blood tests to monitor the levels of galactose and related metabolites, as well as to assess liver and kidney function.

Clinical evaluations: Physical examinations and clinical assessments are conducted to monitor growth, development, and overall health.

Ophthalmologic assessments: Regular eye examinations are recommended to detect and monitor the development of cataracts, a potential complication of galactosemia.

Genetic Counseling: Family history evaluation: Genetic counselors assess the family history of galactosemia to determine the likelihood of inheriting the disorder.

Education and support: Genetic counselors provide information about the inheritance pattern, genetic testing options, and the implications of galactosemia for family planning. They offer emotional support and resources to individuals and families affected by galactosemia.

Research and advancements: Ongoing research aims to deepen the understanding of galactosemia, develop improved diagnostic techniques, explore potential treatments, and enhance the quality of life for individuals with the condition.

It’s important to note that the specific methods and materials utilized may vary depending on the individual’s age, severity of the condition, and healthcare provider recommendations [7]. Consulting with healthcare professionals experienced in managing galactosemia is crucial for personalized treatment plans and guidance.

Results and Discussion

The analysis included four prepubescent females with classic galactosemia, ages 6 to 11. Tanner staging, follicle density, genotype, demographic data, and baseline blood hormone levels were gathered and reported. Follicles were noted to be available beyond the cortex and inside the medulla. Patients were identical siblings with the same GALT gene pathogenic homozygous variant.

The results and discussion of galactosemia typically revolve around the outcomes of the management strategies, the impact on the individual’s health and development, and ongoing research in the field. Here are some key points that may be addressed in the results and discussion of galactosemia:

Effectiveness of dietary modifications

Success of galactose-free diet: The primary goal of dietary modifications is to eliminate galactose and lactose from the individual’s diet [8]. The results may discuss the effectiveness of adhering to a galactose-free diet in preventing complications and promoting healthy growth and development.

Nutritional status: The impact of the galactose-free diet on the individual’s nutritional status may be assessed, including monitoring for deficiencies and evaluating growth parameters.

Compliance challenges: Discussion may focus on the challenges faced by individuals and families in maintaining a strict galactose-free diet, including dietary restrictions, social implications, and practical considerations.

Complications and long-term outcomes

Evaluation of complications: The discussion may address the incidence and severity of complications associated with galactosemia, such as liver damage, kidney problems, cataracts, and neurodevelopmental issues.

Impact on quality of life: The results may explore the overall impact of galactosemia on the individual’s quality of life, including factors such as educational outcomes, social interactions, and psychological wellbeing.

Identification of subtypes: Galactosemia is a heterogeneous disorder with different subtypes caused by specific enzyme deficiencies [9]. The discussion may highlight any differences in outcomes and complications based on the subtype of galactosemia.

Ongoing research and future directions

Advances in treatment options: The discussion may cover emerging research and potential therapies beyond dietary modifications, such as enzyme replacement therapy, gene therapy, or pharmacological interventions.

Improved diagnostic techniques: The results may address the development of more sensitive and efficient diagnostic methods, including genetic testing approaches, that aid in early and accurate diagnosis of galactosemia.

Long-term follow-up studies: Discussion may focus on the need for long-term follow-up studies to assess the health and well-being of individuals with galactosemia as they transition into adulthood and beyond.

Support and advocacy: The importance of continued support networks, resources, and advocacy for individuals and families affected by galactosemia may be emphasized in the discussion [10].

It’s worth noting that the results and discussion section can vary based on the specific research study or clinical evaluation being conducted, and may also incorporate findings from relevant literature and previous studies.

Conclusion

Low AMH in all of our patients suggests low ovarian reserve. All four patients had significant follicle density values on histologic analysis, indicating the presence of follicles despite low AMH. In patients with galactosemia, there may be a discrepancy between AMH values and actual follicle density, and AMH may not be as accurate a screening marker for ovarian reserve in this patient population. Last but not least, people with galactosemia may benefit greatly from over-the-counter fertility treatments.

In conclusion, galactosemia is a rare genetic disorder characterized by the body’s inability to metabolize galactose properly due to enzyme deficiencies. It is typically diagnosed through newborn screening programs, enabling early intervention and management. The primary treatment approach involves strict adherence to a galactose-free diet, which eliminates galactose and lactose from the individual’s diet.

Through proper dietary modifications and medical monitoring, individuals with galactosemia can lead relatively normal lives. Adhering to a galactose-free diet helps prevent complications such as liver damage, kidney problems, cataracts, intellectual disability, and developmental delays. Regular blood tests, clinical evaluations, and ophthalmologic assessments are important for monitoring the individual’s health and detecting any potential issues.

Genetic counseling plays a crucial role in supporting families with a history of galactosemia. It provides education about the inheritance pattern, offers guidance on family planning, and ensures emotional support for affected individuals and their families.

Ongoing research continues to advance our understanding of galactosemia, aiming to improve diagnostic techniques, explore new treatment options beyond dietary modifications, and enhance the overall quality of life for individuals with the condition. This research highlights the importance of continued support networks, resources, and advocacy to raise awareness and provide necessary assistance to individuals and families affected by galactosemia.

With early diagnosis, proper management, and ongoing medical care, individuals with galactosemia can live fulfilling lives, minimizing the impact of the condition and maximizing their potential for optimal health and well-being.

Acknowledgement

None

Conflict of Interest

None

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