Phosphoenolpyruvate carboxykinase deficiency

What it is

From: Orphanet

A rare gluconeogenesis disorder characterized by recurrent hypoglycemia mostly associated with acute episodes of severe lactic acidosis and hepatic dysfunction including liver failure due to phosphoenolpyruvate carboxykinase enzyme deficiency. Hypoglycemic seizures occur predominantly at the age of 1-2 years and mostly in the mornings. However they can also present neonatally or at a later age, and could re-occur during school age or adulthood. Patients have recognizable pattern of abnormal urine organicacids (including increased tricarboxylic acid cycle metabolites) and inadequate ketone body production during hypoglycemia. Some patients may also have encephalopathy, cerebral edema and seizures thay may result in neuroregression and/or global developmental delay associated to failure to manage hypoglycemia. Some patients may also be asymptomatic.

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.

Recurrent hypoglycemia · Very frequent (99-80%)

Recurrent episodes of decreased concentration of glucose in the blood.

Elevated circulating alanine aminotransferase concentration · Frequent (79-30%)

An abnormally high concentration in the circulation of alanine aminotransferase (ALT).

Elevated circulating aspartate aminotransferase concentration · Frequent (79-30%)

The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.

Elevated urine fumaric acid level · Frequent (79-30%)

The concentration of fumaric acid in the urine, normalized for urine concentration, is above the upper limit of normal.

Hyperglutaminemia · Frequent (79-30%)

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

Increased circulating lactate concentration · Frequent (79-30%)

Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).

Increased urine alpha-ketoglutarate concentration · Frequent (79-30%)

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

Lactic acidosis · Frequent (79-30%)

An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.

Lacticaciduria · Frequent (79-30%)

An increased concentration of lactic acid in the urine.

Hypoglycemic seizures · Frequent (79-30%)

Decreased liver function · Occasional (29-5%)

Reduced ability of the liver to perform its functions.

Drowsiness · Occasional (29-5%)

Abnormal feeling of sleepiness or difficulty staying awake.

Hepatic steatosis · Occasional (29-5%)

Steatosis is a term used to denote lipid accumulation within hepatocytes.

Hypoglycemic coma · Occasional (29-5%)

Coma induced by low blood sugar.

Other findings in the same source

From: Orphanet

Additional reported features include Hypotonia (Occasional (29-5%)); Lethargy (Occasional (29-5%)); Neurodevelopmental delay (Occasional (29-5%)); Vomiting (Occasional (29-5%)); Acute encephalopathy (Occasional (29-5%)); Neonatal hypoglycemia (Occasional (29-5%)); Hyperammonemia (Very rare (<4-1%)); Microcephaly (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

When it may begin

From: Orphanet

Infancy; Neonatal

Inheritance in the source

From: Orphanet

Autosomal recessive; Mitochondrial inheritance

Frequency and the population described

From: Orphanet

Reported case(s): 10.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

Which doctor should you see?

The suggested department for discussing Phosphoenolpyruvate carboxykinase deficiency 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 Phosphoenolpyruvate carboxykinase deficiency. 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.