NON-KETOTIC HYPERGLYCINEMIA
 
PEDBASE.org - The Pediatric Database - Detailed information of NON-KETOTIC HYPERGLYCINEMIA

 

NON-KETOTIC HYPERGLYCINEMIA

 

DEFINITION:

An inborn error of glycine metabolism characterized by elevated levels of glycine resulting in hypotonia and seizures after birth.

EPIDEMIOLOGY:

  • incidence: ?
  • age of onset:
    • newborn period with lethargy and hypotonia
  • risk factors:
    • familial - autosomal recessive
      • chrom.#: ?
      • genes: ?
    • M = F
    • incidence in northern Finland is 1:12,000

PATHOGENESIS:

1. Background

  • also called Idiopathic Hyperglycinemia
  • the hepatic glycine cleavage enzyme system is a multicomponent system containing 4 enzymes: P-, H-, T-, and L-proteins
  • defects in each one of these enzymes has been identified in patients with Non-Ketotic Hyperglycinemia (NKH)
  • a small group of patients with NKH have a milder more indolent form of the disease characterized by a slower onset of seizures, spasticity, and mental retardation

2. Pathogenesis

  • genetic mutations of the genes coding for any one of the 4 enzymes in the hepatic glycine cleavage enzyme system -> deficient activity of the enzyme system -> accumulation of glycine -> metabolic and central nervous system manifestations

CLINICAL FEATURES:

1. Metabolic Manifestations

  • poor suck and feeding
  • failure to thrive

2. Neurological Manifestations

  • lethargy -> apnea -> coma -> death
  • infantile hypotonia
  • neonatal seizures (usually myoclonic)
  • severe mental retardation
  • microcephaly
  • hiccoughing
  • gross motor developmental delays
  • hypertonia can develop later
  • nystagmus

INVESTIGATIONS:

1. Diagnostic

  • elevated levels of glycine in the plasma, cerebral spinal fluid (CSF), and urine
  • high CSF/plasma glycine ratio
  • deficiency of the hepatic glycine cleavage enzyme system activity on samples collected by liver biopsy
  • prenatal
    • deficiency of the enzyme system activity in cultured chorionic villi

2. Serum

  • some organic acidemias can cause hyperglycinemia (i.e., propionic and methylmalonic acidemias) and should be ruled out by serum and urine amino acid and organic acid determinations
  • normal serum pH with no ketoacidosis

3. EEG

  • diffusely abnormal
  • hypsarrhythmia and/or burst-suppression pattern may be present

4. CT/MRI

  • cerebral atrophy
  • delayed myelination

MANAGEMENT:

1. Supportive

  • multidisciplinary approach
    • Paediatrics, Neurology, PT
    • genetic counselling

2. Medical

1. Convert Glycine to an Excretable Compound

1. Sodium Benzoate

  • conjugates with glycine and excreted as hippuric acid
  • reduces both plasma and CSF glycine concentrations
  • clinical benefit more apparent in milder form of the disease

2. Arginine

  • facilitates the transaminidation of glycine to creatine which is excreted in the urine

2. Dextromethorphan (DM)

  • glycine accumulation in the CNS may stimulate N-methyl-D-asparate (NMDA) receptors leading to increased excitatory activity with subsequent impairment of neuronal functions and synaptic development
  • DM is a NMDA receptor antagonist and may diminish certain neurological manifestations

3. Anticonvulsant Therapy

  • indicated

3. Diet

  • protein restriction may be indicated

4. Prognosis

  • patients usually die in the newborn period
  • those that survive the newborn period are usually severely mentally impaired with seizures and spasticity if not treated medically

ADDITIONAL REFERENCES:

1. Alemzadeh, R., et al., Pediatrics 97(6):924-926 (1996).
2. Hamosh, A., et al., Journal of Pediatrics 121(1):131-135 (1992).

 

 

 

Pediatric Database - NON-KETOTIC HYPERGLYCINEMIA

 

Pediatric Organization - Pedbase [at] Gmail.com

 
1994 -2007 Pedbase.org 

Powered by Database of Pediatrics- NON-KETOTIC HYPERGLYCINEMIA