D-glyceric aciduria

What it is

From: Orphanet

A rare inborn error of metabolism characterized by abnormal urinary excretion of D-glyceric acid due to D-glycerate kinase deficiency. Reported manifestations are highly variable and include a severe encephalopathic picture, chronic metabolic acidosis, developmental delay, intellectual disability, microcephaly, seizures, behavioral abnormalities, as well as only mild speech delay and apparently normal development.

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.

Metabolic acidosis · Very frequent (99-80%)

Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.

Progressive encephalopathy · Very frequent (99-80%)

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.

Floppy infant · Frequent (79-30%)

Floppiness/hypotonia is defined as reduced resistance to passive movement of joints. Physical examination of floppy/hypotonic infants shows head lag, lack of shoulder and elbow muscle contraction on traction response, inability to tighten the shoulder girdle muscles (or slipping through) when held under the axillae, scarf sign (when the arm is pulled to the opposite side, the arm wraps around the neck with the elbow crossing midline), hyperdorsiflexion of the feet, easy apposition of the thumb against the forearm, feet touching the cheek with ease and without discomfort, frog leg position, and inverted U sign on ventral suspension (head, arms, and legs hanging down without elbow or knee flexion and the trunk rounded in a dome shape).

Global developmental delay · Frequent (79-30%)

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.

Hyperglycinemia · Frequent (79-30%)

An elevated concentration of glycine in the blood.

Hyperglycinuria · Frequent (79-30%)

An increased concentration of glycine in the urine.

Increased CSF glycine concentration · Frequent (79-30%)

Abnormally increased levels of glycine in cerebrospinal fluid.

Increased circulating free fatty acid level · Frequent (79-30%)

A higher than normal levels of the fatty acids which can occur in plasma as a result of lipolysis in adipose tissue or when plasma triacyglycerols are taken into tissues.

Intellectual disability · Frequent (79-30%)

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.

Microcephaly · Frequent (79-30%)

Head circumference below 2 standard deviations below the mean for age and gender.

Seizure · Frequent (79-30%)

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.

Spasticity · Frequent (79-30%)

A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.

Other findings in the same source

From: Orphanet

Additional reported features include Autistic behavior (Occasional (29-5%)); Brain atrophy (Occasional (29-5%)); Cerebral visual impairment (Occasional (29-5%)); Chorea (Occasional (29-5%)); Hearing impairment (Occasional (29-5%)); Hypoplasia of the corpus callosum (Occasional (29-5%)); Loss of consciousness (Occasional (29-5%)); Myoclonus (Occasional (29-5%)); Profound global developmental delay (Occasional (29-5%)); Progressive microcephaly (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 D-glyceric aciduria 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 D-glyceric aciduria. 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.