DO: 0061001;
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
Gene/Locus |
Gene/Locus MIM number |
|---|---|---|---|---|---|---|
| 3p21.31 | Glycine encephalopathy 2 | 620398 | Autosomal recessive | 3 | AMT | 238310 |
A number sign (#) is used with this entry because glycine encephalopathy-2 (GCE2) is caused by homozygous or compound heterozygous mutation in the AMT gene (238310), which encodes a member of the glycine cleavage system (protein T), on chromosome 3p21.
Glycine encephalopathy (GCE), also called nonketotic hyperglycinemia (NKH), is an inborn error of metabolism characterized by accumulation of a large amount of glycine in body fluids. Typical cases have severe neurologic features, including seizures, lethargy, and muscular hypotonia soon after birth, and most die with the neonatal period; atypical cases have later onset and less severe psychomotor development (summary by Nanao et al., 1994).
For a general description and a discussion of genetic heterogeneity of glycine encephalopathy, see GCE1 (605899).
Hayasaka et al. (1983) studied the glycine cleavage system in the liver and brain obtained at autopsy in 2 male infants with the typical form of nonketotic hyperglycinemia. In the first infant a defect in the P protein was found; in the second, T protein was defective. The second infant appeared well at birth and nursed well the first day. He was hospitalized on the third day with 'lethargy, bordering on coma.' Despite ventilatory support, 7 exchange transfusions to lower blood glycine, and treatment with sodium benzoate and strychnine, he died on the twentieth day. T protein was undetectable in the brain and extremely low in liver.
Nanao et al. (1994) described patients with GCE caused by mutation in the AMT gene. Patient A was a 19-year-old girl, born of nonconsanguineous Italian parents, with typical GCE. She reportedly had an older affected sister who died at the age of 3 weeks after a classic clinical course. Patient B was a 9-year-old girl, born of nonconsanguineous parents, with atypical GCE. Her development was normal until her second year of life when developmental delay became apparent. Her deceased older sister also had atypical GCE. Patient B and her sister were previously reported by Haan et al. (1986)
Kure et al. (1998) reported 14 children with typical GCE in a consanguineous Israeli-Arab kindred. All of the patients had seizures and respiratory failure within 2 days after birth, and all had a mutation in the AMT gene.
The transmission pattern of GCE2 in the families reported by Nanao et al. (1994) was consistent with autosomal recessive inheritance.
In a 19-year-old girl (patient A) with typical GCE2, Nanao et al. (1994) identified a homozygous missense mutation in the AMT gene (G269D; 238310.0001). Her parents and an unaffected sib were heterozygous for the mutation. In a 9-year-old girl (patient B) and her deceased sister with atypical GCE2, previously reported by Haan et al. (1986), Nanao et al. (1994) identified compound heterozygous mutations in the AMT gene (G47D, 238310.0002 and R320H, 238310.0006).
In 14 affected members of a consanguineous Israeli-Arab kindred with typical GCE2, Kure et al. (1998) identified a homozygous missense mutation in the AMT gene (H42R; 238310.0003).
Haan, E. A., Kirby, D. M., Tada, K., Hayasaka, K., Danks, D. M. Difficulties in assessing the effect of strychnine on the outcome of non-ketotic hyperglycinaemia: observations on sisters with a mild T-protein defect. Europ. J. Pediat. 145: 267-270, 1986. [PubMed: 3769993] [Full Text: https://doi.org/10.1007/BF00439398]
Hayasaka, K., Tada, K., Kikuchi, G., Winter, S., Nyhan, W. L. Nonketotic hyperglycinemia: two patients with primary defects of P-protein and T-protein, respectively, in the glycine cleavage system. Pediat. Res. 17: 967-970, 1983. [PubMed: 6336599] [Full Text: https://doi.org/10.1203/00006450-198312000-00008]
Kure, S., Mandel, H., Rolland, M.-O., Sakata, Y., Shinka, T., Drugan, A., Boneh, A., Tada, K., Matsubara, Y., Narisawa, K. A missense mutation (his42arg) in the T-protein gene from a large Israeli-Arab kindred with nonketotic hyperglycinemia. Hum. Genet. 102: 430-434, 1998. [PubMed: 9600239] [Full Text: https://doi.org/10.1007/s004390050716]
Nanao, K., Okamura-Ikeda, K., Motokawa, Y., Danks, D. M., Baumgartner, E. R., Takada, G., Hayasaka, K. Identification of the mutations in the T-protein gene causing typical and atypical nonketotic hyperglycinemia. Hum. Genet. 93: 655-658, 1994. [PubMed: 8005589] [Full Text: https://doi.org/10.1007/BF00201565]