Nonketotic Hyperglycinemia

Abstract

Nonketotic hyperglycinemia is a rare metabolic disorder with severe, frequently fatal, neurologic manifestations. Reliable and accurate diagnosis depends on careful interpretation of laboratory findings. The clinical suspicion should lead to determination of glycine in plasma and cerebrospinal fluid. Amino acid analysis presents diagnostic values for classic nonketotic hyperglycinemia, but it also should be performed in suspected cases of atypical nonketotic hyperglycinemia and in children with seizures, failure to thrive, behavior problems, and uncoordinated movements. Clinical assessment should be reinforced by demonstration of elevated cerebrospinal fluid-to-plasma glycine ratio. Confirmatory diagnosis requires enzymatic and genetic investigation of glycine cleavage system. An early diagnosis, though not affecting clinical outcome, allows proper genetic counseling, with the possibility of prenatal diagnosis. We report 3 cases of nonketotic hyperglycinemia, 2 typical neonatal and 1 atypical, diagnosed in Pediatric Hospital of Coimbra, Portugal, and investigated at Laboratory of Biochemical Genetics in 2004 to 2010 (incidence 1:47 455; prevalence 1:782 951).

Clinical, Laboratory, and Short-Term Outcomes in Neonatal Nonketotic Hyperglycinemia

“…There is no current effective treatment option which can change the disease prognosis (10,18). In literature, in contrast to studies that do not recommend diet treatment because glycine is a non-essential amino acid, there are other studies reporting that a limited protein diet can reduce glycine, and thus be used as a part of treatment; but no consensus has been reached on this subject (1,10,18).…”

“…Glycine encephalopathy or nonketotic hyperglycinemia (NKH; Online Mendelian Inheritance in Man-OMIM no. 605899) is a rare, congenital, metabolism disorder with autosomal recessive transmission, which leads to an increase of glycine in all bodily fluids, especially in the central nervous system (CNS) (1). The metabolic defect is a lack of activity in the mitochondrial glycine cleaving enzyme complex (1)(2)(3).…”

“…605899) is a rare, congenital, metabolism disorder with autosomal recessive transmission, which leads to an increase of glycine in all bodily fluids, especially in the central nervous system (CNS) (1). The metabolic defect is a lack of activity in the mitochondrial glycine cleaving enzyme complex (1)(2)(3). There are four forms of NKH, including neonatal, temporary, infantile, and late onset (4).…”

An Infant With Non-Ketotic Hyperglycemia: A Case Report

“…NKH is caused by deficiency in the glycine cleavage system (GCS). Most glycine encephalopathy cases occur during the neonatal period (3,4). The neonatal form manifests in the first hours to days of life with progressive lethargy, hypotonia, myoclonic jerks, hiccups and apnea, which often lead to coma or death (5).…”

Epilepsy of Infancy with Migrating Focal Seizures in a Patient with Nonketotic Hyperglycinemia

“…The typical presentation of NKH is progressive encephalopathy, apnea, and seizures during the neonatal period [2]. Those who survive the neonatal period progress into refractory seizures with moderate to severe cognitive impairment.…”