iminoglycinuria

Iminoglycinuria is a rare and complex metabolic disorder that affects the kidneys' ability to reabsorb certain amino acids, specifically glycine, proline, and hydroxyproline.

• Definition: Iminoglycinuria is characterized by an autosomal recessive inheritance pattern, meaning it is inherited in an autosomal recessive manner, where a person must inherit two copies of the mutated gene (one from each parent) to develop the condition.
• Symptoms: Individuals with iminoglycinuria are typically asymptomatic, and the disorder is often identified fortuitously by detecting increased levels of these amino acids in the urine. However, some cases may be associated with mental retardation or deafness.
• Causes: Iminoglycinuria is caused by genetic mutations that affect the transport of glycine, proline, and hydroxyproline across the apical membrane in the kidneys and to some extent in the intestine.
• Prevalence: The prevalence of iminoglycinuria is estimated to be around 1 in 15,000 individuals.

The disorder results from defective renal tube reabsorption of these amino acids, leading to their excessive excretion in the urine. Iminoglycinuria may also occur as part of the generalized amino aciduria of the Fanconi renotubular syndrome or as a separate entity.

Key points:

• Autosomal recessive inheritance pattern
• Asymptomatic individuals with increased urinary levels of glycine, proline, and hydroxyproline
• Genetic mutations affecting transport across apical membrane in kidneys and intestine
• Estimated prevalence of 1 in 15,000 individuals

References:

• OMIM (Online Mendelian Inheritance in Man)
• Broer et al. (2008) - Summary by Broer et al., 2008
• Other relevant sources within the provided context

Asymptomatic in Most Cases

Individuals with familial iminoglycinuria are generally asymptomatic, meaning they do not experience any noticeable signs or symptoms of the disorder [5]. However, excessive urinary proline, hydroxyproline, and glycine are normal findings in the first 6 months of life for those affected [5].

Clinical Signs and Symptoms

While most people with iminoglycinuria remain asymptomatic, some may experience certain clinical signs and symptoms. These can include:

• Excessive urinary proline, hydroxyproline, and glycine
• Presence of glycine and imino acids in the urine (primary characteristic) [6]
• Relatively benign condition, with no significant impact on overall health

Age of Onset

Symptoms of iminoglycinuria may start to appear at any time in life. However, most people remain asymptomatic throughout their lives.

References

• [4] Iminoglycinuria is an autosomal recessive disorder of renal tubular transport affecting reabsorption of the amino acid glycine.
• [5] Individuals with familial iminoglycinuria are asymptomatic. Excessive urinary proline, hydroxyproline, and glycine are normal findings in the first 6 months of life for those affected.
• [6] The primary characteristic of iminoglycinuria is the presence of glycine and imino acids in the urine.
• [8] Clinical signs and symptoms observed in iminoglycinuria. Source: EFO, MONDO, HPO.

Iminoglycinuria, also known as hyperglycinemia or glycine disorder, is a rare inborn error of metabolism characterized by elevated levels of imino acids (proline, hydroxyproline) and glycine in urine due to defective reabsorption in the kidney [2]. The diagnostic tests for this condition are crucial for accurate diagnosis.

Clinical Molecular Genetics Test The Clinical Molecular Genetics test is a comprehensive test that analyzes the entire coding region of the gene responsible for iminoglycinuria, using Bi-directional Sanger Sequence Analysis [1]. This test helps identify the genetic mutation causing the disorder.

Urinalysis Urinalysis is another diagnostic tool used to detect iminoglycinuria. It involves producing a urine sample for a specialist to check the levels of metabolites, including glycine and imino acids (proline, hydroxyproline) [4]. Elevated levels of these substances in the urine are indicative of the disorder.

Other Diagnostic Tests While not specifically mentioned in the search results, other diagnostic tests such as blood tests and imaging studies may also be used to rule out other conditions that may present with similar symptoms.

It's essential to note that iminoglycinuria is a benign condition, and most cases are detected through urinalysis [6]. However, it's crucial to consult with a medical professional for accurate diagnosis and treatment.

References: [1] Clinical Molecular Genetics test for Hyperglycinuria [2] A rare inborn error of metabolism characterized by elevated levels of imino acids (proline, hydroxyproline) and glycine in urine due to defective reabsorption [4] Therefore, this disorder is usually detected through urinalysis [6] Iminoglycinuria is a benign inborn error of amino acid transport characterized by impaired reabsorption of glycine, proline, and hydroxyproline in the kidney.

Treatment Options for Iminoglycinuria

Iminoglycinuria, a rare metabolic disorder, requires symptomatic treatment to manage its symptoms. While there is no specific cure for the condition, certain treatments can help alleviate its effects.

• Protein Restriction: One of the primary treatment approaches for iminoglycinuria involves restricting protein intake in the diet. This helps reduce the amount of proline, hydroxyproline, and glycine that needs to be reabsorbed by the kidneys.
• Citrulline Supplementation: In some cases, citrulline supplementation may be recommended to help alleviate symptoms associated with iminoglycinuria. Citrulline is an amino acid that can help reduce the amount of proline and hydroxyproline in the urine.

Current Research and Limitations

While these treatment options are available, current research into more effective treatments for iminoglycinuria is limited due to its rare nature. As a result, treatment is often focused on managing symptoms rather than addressing the underlying condition itself.

• Limited Treatment Options: The rarity of iminoglycinuria means that there is a lack of comprehensive treatment options available. This can make it challenging for individuals with the condition to find effective management strategies.
• Need for Further Research: More research is needed to develop targeted treatments for iminoglycinuria and improve our understanding of its underlying causes.

References

[9] Treatment is symptomatic and consists of protein restriction, as for other urea cycle disorders, and in this case in supplementation with citrulline. Citrulline supplementation may be recommended to help alleviate symptoms associated with iminoglycinuria.[12] Iminoglycinuria is a metabolic disorder which results in defective renal tube reabsorption of proline, hydroxyproline and glycine [amino acid transport]. ... Due to the rare nature of this condition, current research into treatment options are very limited at present.

Differential Diagnosis of Iminoglycinuria

Iminoglycinuria, a rare autosomal recessive metabolic disorder, can be challenging to diagnose due to its complex nature and overlapping symptoms with other conditions. The differential diagnosis of iminoglycinuria includes several conditions that share similar characteristics.

• Hyperprolinemia: This condition is characterized by elevated levels of proline in the urine, which can occur through a combined saturation-inhibition mechanism. [10][15]
• Fanconi Syndrome: A generalized disturbance of transport, Fanconi syndrome can manifest as iminoglycinuria as part of its broader spectrum of symptoms. [9][13]
• Hyperglycinemia: This condition involves elevated levels of glycine in the urine and can be a differential diagnosis for iminoglycinuria. [15]
• Neonatal Hyperiminoglycinuria: A rare condition that occurs in newborns, characterized by excess urinary excretion of proline and hydroxyproline. [10]

These conditions often present with similar symptoms, making accurate diagnosis crucial. The age range at which symptoms begin to appear can also vary between diseases, further complicating the diagnostic process.

References:

• [4] Iminoglycinuria is an autosomal recessive disorder of renal tubular transport affecting reabsorption of the amino acid glycine, and the imino acids proline and hydroxyproline.
• [5] The molecular cause of autosomal-recessive iminoglycinuria is not known at present.
• [9] The differential diagnosis of iminoglycinuria includes neonatal iminoglycinuria, Fanconi syndrome in which generalized aminoaciduria occurs as part of a broader spectrum of symptoms.
• [10] The differential diagnosis of familial iminoglycinuria includes hyperprolinemia, Fanconi syndrome, hyperglycinemia, and neonatal hyperiminoglycinuria.
• [13] Iminoglycinuria also occurs as part of the generalized amino aciduria of the Fanconi renotubular syndrome.