|
NON-KETOTIC
HYPERGLYCINEMIA |
o
Non-ketocic
hyperglycinemia is an unusual autosomal recessive disorder of glycine metabolism
in which large amounts of glycine accumulate in body fluids and especially in
cerebrospinal fluid.
o
1:50 000
births.
o
Glycine
is a neurotransmitter amino acid that is usually broken down by a mitochondrial
multienzyme cleavage system presenting four individual components:
§
P-protein
(more than 80% of affected individuals have defects in the structure of the
P-protein).
§
H-protein,
§
T-protein
and
§
L-protein
(1).
o
The
cleavage system is specifically expressed in the liver, the kidneys and the
brain
o
A
reduction by 50% of glycinemia is sufficient to protect the fetal brain in
heterozygous mothers (2) and maternal cleavage enzymatic activity produces
variable glycine accumulation, the consequences of which on fetal brain
development can vary. Deficiency or immaturity in the glycine cleavage system
and particularly deficiency of P-protein may also explain why some fetuses are
affected rather than others.
o
Diagnosis
of non-ketotic hyperglycinemia can be carried out on a liver biopsy and/or cerebrospinal
fluid with markedly elevated glycine levels in the cerebrospinal fluid,
although serum glycine levels can be normal (3).
o
One
third of these children die during the neonatal period and those who survive
develop spastic tetraplegia associated with severe mental retardation.
o
No
known treatment options at this stage.
ULTRASOUND |
§
Hypoplasia
of the corpus callosum and non-ketotic hyperglycinemia is known and has
previously been described postnatally (4-6). The differntial diagnosis
includes: propionic acidemia, methyl malonic acidemia, maternal phenylketonuria
and even anomalies of the Krebs cycle such as fumarase deficiency and pyruvate
dehydrogenase or decarboxylase deficiency (7).
§
Link
to the Ultrasound of callosal agenesis.
§
Dobyns'
postnatal study (8).
·
a
cerebral anomaly was present in 10 of 15 cases of non-ketotic hyperglycinemia
·
corpus
callosum was abnormal in six, including complete agenesis in three cases,
partial agenesis in one and hypoplasia in two.
REFERENCES |
1.
Tada K, Hayasaka K. Nonketotic hyperglycinemia; clinical and
biochemical aspects. Eur J Pediatr
1987; 146: 221-227
2.
Kolodny EH. Agenesis of the corpus callosum: a marker for
inherited metabolic disease. Neurol
1989; 39: 847-848
3.
Agamanolis DP, Potter JL, Lunsdgren DW. Neonatal glycine
encephalopathy; biochemical and neuropathologic findings. Pediatr Neurol 1993; 9: 140-143
4.
Press GA, Barshop BA, Haas RH, Nyhan WL, Glass RF, Hesselink
JR. Abnormalities of the brain in nonketotic hyperglycinemia. Am J Neuroradiol 1989; 10: 315-321
5.
Rogers T, Al-Rayess M, O'Shea P, Ambler MW. Dysplasia of the
corpus callosum in identical twins with nonketotic hyperglycinemia. Pediatr Pathol 1991; 11: 897-902
6.
Wariyar UK, Welch RJ, Milligan DW, Perry RH. Sonographic and
pathologic features of callosal hypoplasia in nonketotic hyperglycinemia. Arch Dis Child 1990; 65: 670-671
7. De Meirleir L, Lissens W, Denis R, Wayenberg JL, Michotte A, Brucher JM, Vamos E, Gerlo E, Liebaers I. Pyruvate dehydrogenase deficiency; clinical and biochemical diagnosis. Pediatr Neurol 1993; 9: 216-220
8. Dobyns WB. Agenesis of the corpus callosum and gyral malformations are frequent manifestations of nonketotic hyperglycinemia. Neurology 1989; 39: 817-820