How do untreated inherited metabolic conditions affect weight gain?

From the Guidelines

Untreated inherited metabolic conditions can significantly impact weight gain through various mechanisms, and early diagnosis and appropriate treatment are essential to manage these disorders and normalize weight patterns. These disorders disrupt normal metabolic processes, often leading to abnormal weight patterns. For example, conditions like hypothyroidism can slow metabolism and cause weight gain, while disorders like phenylketonuria (PKU) may require strict dietary management to prevent complications 1. Untreated galactosemia can cause failure to thrive and poor weight gain in infants. Glycogen storage diseases can lead to enlarged liver and abnormal fat distribution. Fatty acid oxidation disorders may cause low blood sugar and poor growth. Mitochondrial disorders often result in failure to gain weight appropriately due to cells' inability to produce sufficient energy. Lysosomal storage diseases can cause organ enlargement that appears as weight gain in certain body areas.

The specific impact varies by condition, but most metabolic disorders affect weight by altering energy production, nutrient processing, or hormone regulation. According to a study published in Circulation in 2016, lifestyle modification, including a low-caloric diet and physical exercise, is first-line therapy for managing comorbidities of hypertension, obesity, diabetes mellitus, hyperlipidemia, and metabolic syndrome in chronic heart failure 1. A realistic weight loss goal is a 7% to 10% reduction in baseline weight over 6 to 12 months.

Key considerations for managing weight gain in inherited metabolic conditions include:

• Early diagnosis and treatment
• Special diets, such as a low-caloric diet with low intake of saturated fats, trans-fatty acids, cholesterol, and simple carbohydrates, and an increased consumption of fruits, vegetables, and whole grains
• Enzyme replacement therapy or medications specific to the condition
• Regular exercise, such as a minimum of 30 min of daily moderate physical activity
• Monitoring and management of comorbidities, such as hypertension, diabetes, and hyperlipidemia.

As noted in the 2007 guidelines for the management of arterial hypertension, a reduction in body weight by low caloric diet and physical exercise is the first and main treatment strategy in subjects with the metabolic syndrome 1. A combination of a blocker of the renin-angiotensin system and a calcium antagonist may be considered for blood pressure management. Overall, a comprehensive approach to managing inherited metabolic conditions is crucial to preventing weight gain and related complications, and improving quality of life.

From the FDA Drug Label

It has been shown to facilitate long-chain fatty acid entry into cellular mitochondria, thereby delivering substrate for oxidation and subsequent energy production. Primary systemic carnitine deficiency is characterized by low concentrations of levocarnitine in plasma, RBC, and/or tissues The literature reports that carnitine can promote the excretion of excess organic or fatty acids in patients with defects in fatty acid metabolism and/or specific organic acidopathies that bioaccumulate acylCoA esters. CARNITOR® may alleviate the metabolic abnormalities of patients with inborn errors that result in accumulation of toxic organic acids

The effect of untreated inherited metabolic conditions on weight gain is not directly addressed in the provided drug label. Inherited metabolic conditions can lead to accumulation of toxic organic acids and disruption of intermediary metabolism, but the label does not explicitly state how this affects weight gain. Therefore, no conclusion can be drawn about the relationship between untreated inherited metabolic conditions and weight gain based on this information 2.

From the Research

Untreated Inherited Metabolic Conditions and Weight Gain

• Untreated inherited metabolic conditions can have various effects on the body, including weight gain, due to the accumulation of toxic substances or the inability to properly metabolize nutrients 3, 4.
• Inherited metabolic disorders can lead to metabolic decompensations and chronic organ-specific complications, even in adults, which may contribute to weight gain 3.
• Dietary therapy is a crucial aspect of managing inherited metabolic disorders, and improper management can lead to weight gain or other metabolic problems 4.
• The lack of tailored treatment and coordinated monitoring of target organs can exacerbate the effects of inherited metabolic conditions, potentially leading to weight gain and other complications 3, 5.
• Inherited metabolic disorders can manifest in diverse ways, and knowledge of these disorders and their pathophysiology is essential for providing proper care and managing weight gain and other related issues 6.
• Neuroimaging and other diagnostic tools can aid in the diagnosis and management of inherited metabolic disorders, which is critical for preventing or managing weight gain and other complications 7.