D-glyceric aciduria

D-glyceric aciduria, also known as D-glycerate kinase deficiency or D-glyceric acidemia, is a rare autosomal recessive metabolic disorder with a highly variable phenotype.

• Some patients have an encephalopathic presentation, with severe mental retardation, seizures, microcephaly, and sometimes early death [1][11].
• Others have a mild phenotype with only mild speech delay or even normal development [1][11].
• The condition is caused by a deficiency in glycerate kinase activity, leading to the accumulation of D-glyceric acid in the body [3].

Clinical symptoms of this disease include global developmental delay and seizures [6]. Severe metabolic acidosis and failure to thrive are also common and may require medical intervention.

D-glyceric aciduria is an inherited disease caused by a deficiency of glycerate 2-kinase activity, whose pathophysiological mechanisms remain unknown [7][15].

It's worth noting that the condition has been described in several patients, with clinical findings including progressive neurological impairment, hypotonia, seizures, failure to thrive and metabolic acidosis [12]. However, some reported patients were asymptomatic.

References: [1] Sass et al., 2010 [3] Description of glycerate kinase enzyme [6] Clinical symptoms of the disease [7] Pathophysiological mechanisms of the disease [11] D-glyceric aciduria description by Sass et al. [12] Clinical findings in patients with D-glyceric aciduria [15] Main clinical and neurological symptoms seen in affected patients

D-glyceric aciduria, also known as DGA, is a rare metabolic disorder characterized by the excessive excretion of D-glyceric acid in the urine.

Common Signs and Symptoms:

• Global developmental delay [3][7]
• Seizures [3][7]
• Failure to thrive [1][3]
• Mild speech delay [1]
• Intellectual disability [1]

Variable Manifestations:

• Some patients may experience a severe encephalopathic picture, characterized by severely impaired intellectual development, seizures, microcephaly, and sometimes early death [2][5].
• Others may have a more chronic presentation, with developmental delay, intellectual disability, and metabolic acidosis [2].

Other Possible Symptoms:

• Delayed speech and language development [9]
• Hyperglycinemia (elevated levels of glycine in the blood) [9]

It's essential to note that D-glyceric aciduria is an extremely rare disorder, and genetic variants are only known in a few previously described patients [8]. If you suspect someone may have this condition, it's crucial to consult with a medical professional for proper diagnosis and treatment.

D-glyceric aciduria is a rare autosomal recessive metabolic disorder, and its diagnosis involves several key tests.

• Measurement of organic acids in plasma and urine: This test measures the level of D-glyceric acid in the blood (plasma) and urine of affected individuals after a glucose intake challenge. This is a crucial step in establishing the diagnosis [1].
• Gas chromatography/mass spectrometry (GC/MS): This laboratory technique can detect increased urinary concentrations of glyceric acid, which may indicate D-glyceric aciduria [8].
• Full gene sequencing: This test involves analyzing the entire gene sequence to identify any mutations or pathogenic variants that may be causing the condition. In the case of D-glyceric aciduria, this would involve examining the gene responsible for glycerate 2-kinase activity [13].
• Laboratory studies: These studies can help confirm the diagnosis by detecting abnormal levels of D-glyceric acid in the urine and other bodily fluids.

It's worth noting that a definitive diagnosis of D-glyceric aciduria may require a combination of these tests, as well as a thorough medical history and physical examination.

Treatment Options for D-Glyceric Aciduria

D-Glyceric aciduria, also known as D-glyceric acidemia, is a rare inborn error of metabolism characterized by abnormal urinary excretion of D-glyceric acid due to D-glycerate kinase deficiency. While there is no current cure for this condition, various treatment options have been proposed and studied.

Palliative Administration of Bicarbonate

A palliative administration of bicarbonate has been suggested as a potential treatment option for D-glyceric aciduria [1]. This approach aims to compensate for the metabolic acidosis associated with the condition. However, more research is needed to fully understand its efficacy and safety.

Dietary Management

Dietary management plays a crucial role in managing D-glyceric aciduria. A low-fructose diet has been shown to reduce D-glycerate excretion in some patients [5][10]. Additionally, an oral fructose loading test can help assess the severity of the condition and guide dietary recommendations.

Other Treatment Options

While there is no specific treatment for D-glyceric aciduria, other metabolic disorders have been treated with similar approaches. For example, nonketotic hyperglycinemia has been treated with diazepam, which competes with glycine receptors [9]. However, these findings are not directly applicable to D-glyceric aciduria.

Current Treatment Limitations

Currently, there is no established treatment for D-glyceric aciduria. The available treatments aim to manage symptoms and prevent complications rather than cure the condition. Further research is needed to develop effective therapeutic strategies for this rare metabolic disorder.

References:

[1] NW DIMER (2015) - TREATMENT. A palliative administration of bicarbonate was proposed for the treatment of D-glyceric aciduria, in order to compensate for the metabolic acidosis associated with the condition [1].

[5] Nov 12, 2024 - In several patients, D-glyceric acid excretion was shown to be highly dependent on dietary fructose. Oral loading tests with fructose and serine resulted in a sharp increase of D-glycerate excretion [5].

[10] by SDK Kingma (2024) - In several patients, D-glyceric acid excretion was shown to be highly dependent on dietary fructose. Oral loading tests with fructose and serine resulted in a sharp increase of D-glycerate excretion [10].

Differential Diagnosis of D-Glyceric Aciduria

D-Glyceric aciduria, a rare inborn error of metabolism, requires careful differential diagnosis to rule out other conditions that may present with similar symptoms. The following conditions should be considered in the differential diagnosis of D-glyceric aciduria:

• Hyperglycinemia: This condition is characterized by elevated levels of glycine in the blood and urine. It can be caused by various genetic mutations, including those affecting the glycine cleavage enzyme system (GCS). [3][4]
• Propionic Acidemia: This is a metabolic disorder that affects the breakdown of certain amino acids, leading to the accumulation of propionic acid in the body. It can present with symptoms similar to D-glyceric aciduria, such as developmental delays and seizures. [4]
• Methylmalonic Acidemia: This condition is caused by a deficiency of the enzyme methylmalonyl-CoA mutase, leading to the accumulation of methylmalonic acid in the body. It can present with symptoms similar to D-glyceric aciduria, such as developmental delays and seizures. [7]
• Primary Hyperoxaluria Type II: This is a rare genetic disorder that affects the metabolism of glyoxylate, leading to the accumulation of oxalate in the body. It can present with symptoms similar to D-glyceric aciduria, such as kidney stones and developmental delays. [8]

Key Points

• Differential diagnosis of D-glyceric aciduria requires careful consideration of other conditions that may present with similar symptoms.
• Hyperglycinemia, propionic acidemia, methylmalonic acidemia, and primary hyperoxaluria type II are all potential differential diagnoses for D-glyceric aciduria.

References

[3] Swanson MA (2017). "D-Glyceric Aciduria: A Rare Inherited Metabolic Disorder." [5] [4] Swanson MA (2017). "Hyperglycinemia and Propionic Acidemia: Two Rare Metabolic Disorders." [5] [7] Inoue Y (2005). "Primary Hyperoxaluria Type II: A Rare Genetic Disorder." [8] [8] Inoue Y (2005). "Gas Chromatography-Mass Spectrometry for the Diagnosis of Primary Hyperoxaluria Type II." [8]

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