Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency

Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency is a rare genetic disorder characterized by an inability to break down a specific amino acid, proline, due to a deficiency in the enzyme delta-1-pyrroline-5-carboxylate dehydrogenase (P5CDH). This condition falls under the broader category of amino acid metabolism disorders and specifically affects the proline degradation pathway, leading to an accumulation of pyrroline-5-carboxylate (P5C) and proline in the body. The disorder is inherited in an autosomal recessive manner, meaning that an individual must inherit two copies of the mutated gene, one from each parent, to be affected.

Symptoms and Diagnosis

The clinical presentation of delta-1-pyrroline-5-carboxylate dehydrogenase deficiency can vary widely among affected individuals. Symptoms may include intellectual disability, seizures, hypotonia (decreased muscle tone), and metabolic acidosis (an increase in acidity in the blood and body tissues). Some patients may also exhibit physical features such as microcephaly (a smaller than normal head size) and failure to thrive.

Diagnosis of this condition typically involves biochemical testing to detect elevated levels of proline and P5C in the blood and urine. Genetic testing can confirm the diagnosis by identifying mutations in the ALDH4A1 gene, which encodes the P5CDH enzyme.

Treatment and Management

There is no cure for delta-1-pyrroline-5-carboxylate dehydrogenase deficiency, and treatment is primarily supportive and symptomatic. Management strategies may include dietary restrictions to limit proline intake and supplementation with vitamins and minerals to support overall health. Regular follow-up with a team of healthcare providers, including a geneticist, neurologist, and dietitian, is important to monitor the condition and adjust treatment as necessary.

Genetics

Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency is caused by mutations in the ALDH4A1 gene. This gene provides instructions for making the enzyme necessary for the final step in the degradation pathway of proline to glutamate, an important neurotransmitter and metabolic intermediate. Mutations in ALDH4A1 lead to a functional deficiency of the P5CDH enzyme, disrupting normal proline metabolism and resulting in the accumulation of toxic intermediates.

Epidemiology

As a rare genetic condition, the exact prevalence of delta-1-pyrroline-5-carboxylate dehydrogenase deficiency is unknown. It has been reported in a small number of individuals worldwide, with no apparent ethnic or geographical predilection.

See Also

• Amino acid metabolism disorder
• Autosomal recessive inheritance
• Metabolic acidosis
• Genetic testing

Delta-1-pyrroline-5-carboxylate dehydrogenase deficiency Resources
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