What Is Hyperprolinemia Type II?

Hyperprolinemia is a rare genetic condition affecting people with a genetic mutation. Although rare, it is important to learn about Hyperprolinemia type 2 as this will allow for early diagnosis and improved quality of life for affected people. This short but informative article will highlight what hyperprolinemia type II is, some common risk factors, signs and symptoms and how it can be diagnosed. 

Introduction

To understand Hyperprolinemia Type 2, it is essential to understand the role of an amino acid called Proline in the body. Proline is considered a “non essential” amino acid which is made from other amino acids in the liver. Proline has many functions and plays important roles in protein formation, development of the brain, and in cellular mechanisms. One of the components of proline is collagen which is important for the function of tendons and joints, and in the development of the brain.

Hyperprolinemia type 2 is a rare inherited disorder of proline metabolism that occurs due to deficiency of the enzyme pyrroline 5 carboxylate dehydrogenase.

Causes and risk factors for hyperprolinemia type 2

Hyperprolinemia Type 2 is a disorder that occurs when there is an abnormality or mutation in the gene ALDH4H. This gene is inherited in an autosomal recessive pattern, meaning that each parent passes down an inactive form of the gene to the child who then develops the condition. Female and male patients are equally affected by the condition as observed by the inheritance pattern showing no preference for a particular sex.

In hyperprolinemia type 2, there is a decrease in pyrroline 5 carboxylate dehydrogenaseresulting in increased levels of pyrroline 5 carboxylate. The accumulation of pyrroline 5 carboxylate then causes more utilisation or inactivation of Pyridoxal Phosphate (PLP), the active form of Vitamin B6.

Signs and symptoms of hyperprolinemia type 2

Hyperprolinemia type 2 occurs as an asymptomatic condition in most cases. Symptoms that have been reported include: 

• Childhood seizures
• Mental disabilities
• Developmental delays

The seizures occurring in childhood may be treated as epilepsy but in reported cases were unresponsive to epileptic medication. In adulthood, the condition is benign but has been linked to certain psychiatric and behavioural issues. However, this has not been extensively studied for the exact correlation.

Diagnosis of hyperprolinemia type 2

Laboratory Tests may be used to diagnose hyperprolinemia, considering that in hyperprolinemia type 2, the levels of proline are increased in body fluids like plasma, cerebrospinal fluid and urine.

• Blood tests to measure serum levels of proline, which may be increased more than 10-fold. The amounts may be 2000 micro mole when the normal range is between 100 to 450 micro mole
• Urine tests carried out may show increased pyrroline 5 carboxylate. The presence of pyrroline 5 carboxylate in urine is diagnostic for hyperprolinemia type 2 and rules out hyperprolinemia type 1
• Genetic testing of DNA strands can be used able to find the mutation of ALDH4H1

Treatment of hyperprolinemia type 2 

The disorder mainly requires no treatment. When treatment is needed, symptoms are treated depending on occurrence. Seizures may respond to anticonvulsants. 

Vitamin B6 supplementation has been shown to improve symptoms in studies. As the condition is rare, there are no protocols advising on dosage.

Restricting proline rich foods has not shown any importance in the management of hyperprolinemia type 2, therefore it is not necessary.

Long-term, Patients with severe presentations may require speech therapy and psychological therapy depending on the presentation.

Outcomes 

The prognosis of hyperprolinemia type 2 is dependent on the symptom severity. Early diagnosis, in symptomatic cases, is important for a good quality of life. Genetic testing allows for identification of family inheritance patterns.Long term monitoring of diagnosed patients is important to analyse any behavioural and mental health issues that have been associated with hyperprolinemia.

FAQ's

What are the different types of hyperprolinemia?

Hyperprolinemia occurs as Inherited which are Type 1 and Type 2 or Acquired (Secondary) hyperprolinemia which is not clearly described but may occur later due to increased dietary intake of proline or an acquired defect in the breakdown of proline.

What is the difference between hyperprolinemia type 1 and type 2?

How is hyperprolinemia diagnosed?

Diagnosis of hyperprolinemia is done by assessment of symptoms if present and testing body fluids like the blood, urine and cerebrospinal fluid for increased levels of proline or pyrroline 5 carboxylate.

Genetic testing can also be done to find the mutation in the gene ALDH1H4.

Summary

In summary, hyperprolinemia is a rare inherited condition caused by the abnormal metabolism of proline. There are two main types of hyperprolinemia which can occur knwon as types 1 and 2. Hyperprolinemia type 2 is a rare disorder inherited in an autosomal recessive pattern.

This condition occurs due to the abnormal breakdown of proline, which leads to increased levels. The deficiency in the enzyme Pyrroline 5 carboxylate dehydrogenase is caused by a mutation in the ALDH4H1 gene.

However, the good news is that there are ways to manage this condition if caught early enough using laboratory tests including blood, urine and DNA tests. It is very important to know about the condition and some of the related symptoms as it can lead to seizures, developmental delays and mental disability. Nevertheless, if ever in doubt, it is always advisable to consult a healthcare professional.