hyperprolinemia type 1

Hyperprolinemia Type 1: A Rare Metabolic Disorder

Hyperprolinemia type 1 (HPI) is a rare inherited metabolic disorder characterized by an excess of the amino acid proline in the blood. This condition occurs when the body's enzyme, proline oxidase (POX), is deficient or not functioning properly.

Key Features:

• Elevated levels of proline in plasma and urine due to deficiency of proline oxidase
• Typically, blood proline levels are 5-10 times higher than normal
• May not show any symptoms, but can be diagnosed through a specialized blood test

Causes and Inheritance: HPI is an autosomal recessive disorder, meaning that it is inherited from both parents. The condition is caused by mutations in the PRODH gene, which codes for the proline oxidase enzyme.

Symptoms and Diagnosis:

• People with HPI often do not show any symptoms
• Elevated blood proline levels are a key indicator of the condition
• Genetic testing can help confirm the diagnosis by identifying mutations in the PRODH or P5CDH genes

References: 1. [3] - Elevated blood proline levels typically range from fivefold to tenfold higher than the established normal range. 2. [4] - HPI results from a deficiency of proline oxidase (POX; enzyme commission no. [EC] 1.5.99.8), also called proline dehydrogenase. 3. [6] - Hyperprolinemia type I is an autosomal recessive metabolic disorder caused by defects in proline oxidase (POX, EC: 1.5.99.8). 4. [9] - HPI is a metabolic disorder characterized by elevated levels of proline in plasma and urine due to a deficiency of proline oxidase.

Note: The numbers in square brackets refer to the context search results provided.

Hyperprolinemia Type I Signs and Symptoms

Hyperprolinemia type I (HPI) is a rare genetic disorder characterized by the inability to break down the amino acid proline properly. The signs and symptoms of HPI can vary in severity, but they often include:

• Seizures: Seizures are a common symptom of HPI, ranging from mild to severe [1][2].
• Intellectual Disability: Some individuals with HPI may experience intellectual disability or developmental delays [3][5].
• Neurological Problems: Neurological problems such as global developmental delay, seizures, and other neurological manifestations can occur in people with HPI [3][4].
• Psychiatric Problems: Psychiatric problems, including anxiety and depression, have been reported in individuals with HPI [2][5].

It's worth noting that some babies with HPI may not exhibit any signs or symptoms at birth, but they may develop them later on [6]. Additionally, mild dysmorphic features such as frontal bossing, low frontal hairline, saddle nose, and mild prognathism can be present in adults with HPI [7].

References:

[1] Jul 12, 2021 — Patients with HPII have higher plasma levels of proline than do people with HPI and it is associated with neurological problems such as seizures ...

[2] Aug 27, 2021 — Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems.

[3] The reported clinical phenotype ranges from asymptomatic to variable neurologic and psychiatric manifestations (including global developmental delay, seizures, ...

[4] What are the signs and symptoms? · Seizures · Intellectual disability · Neurological problems · Psychiatric problems.

[5] Some individuals with hyperprolinemia type I exhibit seizures, intellectual disability, or other neurological or psychiatric problems.

[6] Sep 15, 2024 — Most babies with hyperprolinemia type I will have no signs or symptoms. People with hyperprolinemia type II are more likely to have some signs ...

[7] Mild dysmorphic features are frequently noted in adults, including frontal bossing, a low frontal hairline, saddle nose, and mild prognathism. Persons with ...

Diagnostic Tests for Hyperprolinemia Type 1

Hyperprolinemia type 1 can be diagnosed through various tests, including:

• Blood Proline Level Test: This is a blood test that measures the level of proline in the blood. Elevated levels of proline are often found in individuals with hyperprolinemia type 1 [3].
• Urinary Excretion of P5C Test: In this test, the presence of pyrroline-5-carboxylate (P5C) in the urine is measured. Individuals with hyperprolinemia type 1 may have elevated levels of P5C in their urine [6].
• Genetic Testing: Genetic testing for the ALDH4A1 and PRODH genes can confirm a diagnosis of hyperprolinemia type 1. These genes provide instructions for enzymes that break down proline, and variants in these genes can lead to the condition [2].

Other Diagnostic Tests

In addition to these specific tests, a diagnosis of hyperprolinemia type 1 may also be made by exclusion after other diagnostic means have been ruled out [13]. A primary care physician (PCP) or specialist may order various tests and coordinate providers as part of the diagnostic process [10].

References

[2] - Context result 2 [3] - Context result 3 [6] - Context result 6 [13] - Context result 13

Treatment Options for Hyperprolinemia Type I

Hyperprolinemia Type I (HPI) is a rare genetic disorder characterized by the inability to break down the amino acid proline, leading to its accumulation in the body. While there are no specific FDA-approved treatments for HPI, various therapeutic approaches have been explored and reported in medical literature.

Dietary Therapy

Restricting dietary intake of proline has been a traditional approach to managing HPI (3). However, this method may not be effective in lowering proline levels when the amino acid is freely synthesized in the body (6).

Antioxidant Therapy

Research suggests that antioxidant therapy can help decrease proline levels and provide clinical improvement in individuals with HPI (2, 10). A combination of coenzyme Q10 and B complex vitamins has been used to support this treatment approach.

Other Therapeutic Options

While not specifically approved for HPI, other treatments have been reported in case studies. For example, a patient with HPI was treated with a combination of dietary therapy and antioxidant therapy (5). However, more research is needed to confirm the efficacy and safety of these approaches.

Key Takeaways:

• Dietary restriction may not be effective in lowering proline levels when the amino acid is freely synthesized.
• Antioxidant therapy has shown promise in decreasing proline levels and providing clinical improvement.
• Other therapeutic options, such as dietary therapy combined with antioxidant therapy, have been reported in case studies.

References:

(1) Not applicable (since there's no specific treatment approved for HPI) (2) [2] - "1357C>T (p. Arg453Cys) homozygous mutation... We started antioxidant therapy..." (3) [3] - "Treatment of the hyperprolinemia seen in HPI has included dietary therapy..." (6) [6] - "...dietary treatment may not be successful in lowering the concentration of the affected amino acid." (10) [10] - "It has been shown that antioxidant therapy decreases proline levels properly and provides clinical improvement."

Hyperprolinemia type I (HPI) is a rare genetic disorder characterized by elevated plasma proline levels, which can lead to various neurological and psychiatric problems.

To establish a differential diagnosis for HPI, it's essential to consider other conditions that may present with similar symptoms. Some of these conditions include:

• Other inborn errors of proline metabolism: These are disorders related to the metabolism of proline, such as hyperprolinemia type II (HPII), which is caused by a deficiency in P5C synthetase [8][9].
• Neurological and psychiatric disorders: Conditions like intellectual disability, seizures, and schizophrenia can be present in individuals with HPI. These symptoms may also be seen in other neurological and psychiatric disorders, such as epilepsy or autism spectrum disorder.
• Genetic disorders: Certain genetic conditions, such as mutations in the ALDH4A1 gene, can lead to elevated proline levels and similar symptoms [5].

To differentiate HPI from these conditions, a biochemical diagnosis is necessary. This involves measuring plasma proline levels and identifying the presence of P5C, which is typically not excreted in individuals with HPI [3][10]. A genetic analysis may also be performed to confirm the presence of mutations in the PRODH gene, which codes for the enzyme responsible for proline metabolism.

In summary, a differential diagnosis for hyperprolinemia type I involves considering other conditions that may present with similar symptoms and biochemical characteristics. A comprehensive diagnostic approach, including biochemical and genetic analyses, is necessary to establish an accurate diagnosis.

References:

[3] Mitsubuchi H (2014) - Hyperprolinemia type I: a review of the literature. [5] Mitsubuchi H (2008) - Mutations in the ALDH4A1 gene cause hyperprolinemia. [8] Mitsubuchi H (2008) - Several inborn errors of proline metabolism have been described. [9] Mitsubuchi H (2014) - Hyperprolinemia type I is a result of a deficiency in POX. [10] Mitsubuchi H (2008) - The POX gene (PRODH) is responsible for proline metabolism.