Hyperprolinemia type 2

What it is

From: Orphanet

Hyperprolinemia type 2 is an autosomal recessive proline metabolism disorder due to pyroline-5-carboxylate dehydrogenase deficiency. The condition is often benign but clinical signs may include seizures, intellectual deficit and mild developmental delay.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal enzyme/coenzyme activity · Very frequent (99-80%)

Concentration or activity of an enzyme is above or below the limits of normal in the blood circulation.

Abnormality of the cerebrospinal fluid · Very frequent (99-80%)

An abnormality of the cerebrospinal fluid (CSF).

Atypical behavior · Very frequent (99-80%)

Atypical behavior is an abnormality in a person's actions that can be controlled or modulated by the will of the individual. While abnormal behaviors can be difficult to control, they are distinct from other abnormal actions that cannot be affected by the individual's will.

Global developmental delay · Very frequent (99-80%)

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

Hydroxyprolinuria · Very frequent (99-80%)

An increased concentration of 4-hydroxy-L-proline in the urine.

Hyperprolinemia · Very frequent (99-80%)

The concentration of proline in the blood circulation is above the upper limit of normal.

Increased urine alpha-ketoglutarate concentration · Very frequent (99-80%)

A greater than normal concentration of 2-oxoglutaric acid in the urine.

Intellectual disability · Very frequent (99-80%)

The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence.

Prolinuria · Very frequent (99-80%)

Level of proline in the urine anove the upper limit of normal.

Seizure · Very frequent (99-80%)

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Chronic fatigue · Frequent (79-30%)

Subjective feeling of tiredness characterized by a lack of energy and motivation that persists for six months or longer.

Delayed speech and language development · Frequent (79-30%)

A degree of language development that is significantly below the norm for a child of a specified age.

EEG with generalized sharp slow waves · Frequent (79-30%)

EEG with generalized sharp transient waves of a duration between 80 and 200 msec followed by a slow wave.

Exercise intolerance · Frequent (79-30%)

A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender.

Other findings in the same source

From: Orphanet

Additional reported features include Generalized-onset seizure (Frequent (79-30%)); Hyperalaninemia (Frequent (79-30%)); Hyperglycinemia (Frequent (79-30%)); Increased CSF protein concentration (Frequent (79-30%)); Muscle spasm (Frequent (79-30%)); Reduced circulating vitamin B6 level (Frequent (79-30%)); Sleep abnormality (Frequent (79-30%)); Unsteady gait (Frequent (79-30%)); Abdominal pain (Occasional (29-5%)); Abnormality of eye movement (Occasional (29-5%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

All ages

Inheritance in the source

From: Orphanet

Autosomal recessive

Understanding the inheritance label

From: MedlinePlus Genetics

An autosomal recessive pattern usually involves disease-causing changes in both copies of a gene. Parents may each carry one altered copy without having the condition themselves. A genetic counsellor can explain carrier testing and reproductive implications using the actual laboratory findings, rather than the condition name alone.

Which doctor should you see?

The suggested department for discussing Hyperprolinemia type 2 is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Hyperprolinemia type 2. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.