Transketolase deficiency

What it is

From: Orphanet

A rare disorder of pentose phosphate metabolism characterized by developmental delay and intellectual disability, delayed or absent speech, short stature, and congenital heart defects (such as ventricular septal defect, atrial septal defect, and patent foramen ovale). Additional reported features include hypotonia, hyperactivity, stereotypic behavior, ophthalmologic abnormalities (bilateral cataract, uveitis, strabismus), hearing impairment, and variable facial dysmorphism, among others. Laboratory analysis shows elevated plasma and urinary polyols (erythritol, arabitol, and ribitol) and urinary sugar-phosphates (ribose-5-phosphate and xylulose/ribulose-5-phosphate).

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 heart morphology · Very frequent (99-80%)

Any structural anomaly of the heart.

Elevated circulating ribitol concentration · Very frequent (99-80%)

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

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.

Proportionate short stature · Very frequent (99-80%)

A kind of short stature in which different regions of the body are shortened to a comparable extent.

Absent speech · Frequent (79-30%)

Complete lack of development of speech and language abilities.

Atrial septal defect · Frequent (79-30%)

Atrial septal defect (ASD) is a congenital abnormality of the interatrial septum that enables blood flow between the left and right atria via the interatrial septum.

Attention deficit hyperactivity disorder · Frequent (79-30%)

Attention deficit hyperactivity disorder (ADHD) manifests at age 2-3 years or by first grade at the latest. The main symptoms are distractibility, impulsivity, hyperactivity, and often trouble organizing tasks and projects, difficulty going to sleep, and social problems from being aggressive, loud, or impatient.

Cataract · Frequent (79-30%)

A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.

Compulsive behaviors · Frequent (79-30%)

Behavior that consists of repetitive acts, characterized by the feeling that one "has to" perform them, while being aware that these acts are not in line with one's overall goal.

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.

Hypotonia · Frequent (79-30%)

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

Increased level of ribose in urine · Frequent (79-30%)

An increase in the level of ribose in the urine.

Intellectual disability, mild · Frequent (79-30%)

Mild intellectual disability (ID) is defined as a type of ID characterized by mildly sub-average adaptive functioning and intellectual functioning, with an intelligence quotient (IQ) the range of 50-69.

Uveitis · Frequent (79-30%)

Inflammation of one or all portions of the uveal tract.

Other findings in the same source

From: Orphanet

Additional reported features include Ventricular septal defect (Frequent (79-30%)); Abnormal coronary artery course (Occasional (29-5%)); Abnormal repetitive mannerisms (Occasional (29-5%)); Conjunctivitis (Occasional (29-5%)); Hearing impairment (Occasional (29-5%)); Hepatomegaly (Occasional (29-5%)); Patent ductus arteriosus (Occasional (29-5%)); Patent foramen ovale (Occasional (29-5%)); Renal cyst (Occasional (29-5%)); Seborrheic dermatitis (Occasional (29-5%)). 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

Frequency and the population described

From: Orphanet

Reported case(s): 5.0; Worldwide. This is a published case count, not prevalence. Point prevalence: <1 / 1 000 000; Worldwide; Class only.

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 Transketolase 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 Transketolase 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.