AMINO ACID - NON- KETOTIC HYPERGLYCEMIA PANEL CSF / PLASMA

The AMINO ACID - NON- KETOTIC HYPERGLYCEMIA PANEL CSF / PLASMA measures amino acids, particularly glycine, in paired cerebrospinal fluid and plasma samples. Despite the catalogue wording “hyperglycemia,” this panel is medically intended for the evaluation of nonketotic hyperglycinemia, also called glycine encephalopathy. Hyperglycinemia refers to excessive glycine, whereas hyperglycemia refers to high blood glucose; these are different conditions.

Nonketotic hyperglycinemia is a rare inherited metabolic disorder caused by reduced activity of the glycine cleavage system. When this system does not function properly, glycine accumulates in the blood and central nervous system. Excess glycine in the brain can disrupt normal neurotransmission and lead to serious neurological symptoms. Measuring glycine in simultaneously collected CSF and plasma allows specialists to calculate the CSF-to-plasma glycine ratio, an important biochemical marker used during diagnostic evaluation.

Benefits of the Test

• Quantitatively measures glycine in both CSF and plasma.
• Allows calculation of the CSF-to-plasma glycine ratio.
• Supports diagnosis of nonketotic hyperglycinemia or glycine encephalopathy.
• Helps distinguish NKH from other causes of elevated glycine.
• Guides confirmatory enzyme or molecular genetic testing.
• Supports specialist evaluation of unexplained neonatal or childhood neurological symptoms.

Why Doctors Recommend This Test

A neonatologist, paediatric neurologist, clinical geneticist or metabolic specialist may recommend this panel when a newborn develops severe sleepiness, poor feeding, weak muscle tone, hiccups, breathing pauses, seizures or coma without an obvious cause. Some infants develop symptoms soon after birth, while attenuated forms may present later with developmental delay, seizures, movement abnormalities, behavioural difficulties or intellectual disability.

Plasma glycine may be elevated in NKH, but plasma testing alone cannot reliably establish the diagnosis. Glycine may also increase in other metabolic disorders, after certain medicines or during severe illness. The paired CSF and plasma assessment helps determine whether glycine is disproportionately elevated in the central nervous system. Results are interpreted with the absolute glycine concentrations, calculated ratio, symptoms and other metabolic findings.

Doctors may also request this test to investigate an abnormal newborn-screening or plasma amino acid result. The panel does not replace genetic confirmation. Disease-causing variants involving genes of the glycine cleavage system, commonly GLDC or AMT and less frequently GCSH, may be investigated when the biochemical pattern supports NKH.

Preparation Before Test

CSF is collected through a lumbar puncture performed by a trained medical professional in a hospital or suitable clinical setting. Plasma is obtained from a blood sample. For meaningful calculation of the CSF-to-plasma glycine ratio, both specimens should be collected as close together in time as required by the specialist and laboratory protocol.

Inform the medical team about all medicines, supplements, seizures, recent feeding and existing metabolic diagnoses. Certain medicines, including valproate, may influence glycine metabolism or complicate interpretation. Do not stop any medicine without the treating doctor's advice. Before collection, confirm the required containers, specimen volumes, processing, freezing and transport conditions with the laboratory. Blood contamination of CSF can falsely alter glycine concentration.

Normal Reporting Time

This is a highly specialized paired metabolic analysis and generally requires several working days or longer. Reporting time depends on specimen transportation, sample quality, analytical scheduling, calculation and whether repeat or confirmatory analysis is required. Focus Diagnostics will provide the applicable turnaround estimate before specimen submission.

Who Should Take This Test?

• Newborns with unexplained lethargy, poor feeding, hypotonia, hiccups or breathing abnormalities.
• Infants or children with unexplained seizures or developmental delay.
• Patients with elevated plasma glycine requiring further evaluation.
• Individuals with a clinical pattern suggestive of glycine encephalopathy.
• Siblings or relatives of a person with confirmed nonketotic hyperglycinemia.
• Patients specifically referred by a metabolic specialist, geneticist or neurologist.

Detailed Information

Nonketotic hyperglycinemia is usually inherited in an autosomal recessive pattern. An affected child generally inherits one disease-causing variant from each parent. Parents carrying one altered copy are usually unaffected. When both parents are carriers, each pregnancy has a 25% probability of an affected child, a 50% probability of a carrier child and a 25% probability of a child who inherits neither familial variant.

The CSF-to-plasma glycine ratio is calculated only when the specimens are appropriately paired and concentrations are reported in compatible units. An elevated ratio can support NKH, but the result is not interpreted alone. Blood contamination, specimen timing, medication, illness and laboratory method can affect the values. Age-appropriate and method-specific reference intervals must be used.

Additional investigations may include quantitative plasma amino acids, urine organic acids, acylcarnitine profile, ammonia, lactate, glucose and tests for disorders that can produce secondary hyperglycinemia. Molecular analysis of GLDC, AMT, GCSH or a broader metabolic gene panel may confirm the diagnosis. In selected circumstances, enzyme analysis may also be considered.

Management is individualized and directed by a metabolic specialist. It may include sodium benzoate to reduce glycine concentration, medicines that modify NMDA-receptor activity, seizure treatment, respiratory support, nutrition and developmental therapies. Response varies according to the genetic cause and clinical severity. Early recognition supports appropriate treatment, family counselling and testing options for relatives.