Nonketotic Hyperglycinemia in Tunisia. Report upon a Series of 69 Patients

Abstract

Aim The aim of the study is to report on epidemiological, clinical, and biochemical characteristics of nonketotic hyperglycinemia (NKH) in Tunisia. Methods Patients diagnosed with NKH in Laboratory of Biochemistry at Rabta hospital (Tunis, Tunisia) between 1999 and 2018 were included. Plasma and cerebrospinal fluid (CSF) free amino acids were assessed by ion exchange chromatography. Diagnosis was based on family history, patient's clinical presentation and course, and increased CSF to plasma glycine ratio. Results During 20 years, 69 patients were diagnosed with NKH, with 25 patients originating from Kairouan region. Estimated incidences were 1:55,641 in Tunisia and 1:9,684 in Kairouan. Consanguinity was found for 73.9% of the patients and 42% of the families have history of infantile death due to a disease of similar clinical course than the propositus. Clinical symptoms initiated within the first week of life in 75% of the patients and within the first 3 months in 95.7% ones. The phenotype was severe in 76.8% of the patients. Main symptoms were hypotonia, feeding difficulties, coma, apnea, and seizures. Most patients died within few days to months following diagnosis. CSF to plasma glycine ratio was increased in all patients. CSF and plasma glycine levels were negatively correlated with age of disease onset and severity. Conclusion NKH is quite frequent in Tunisia. Kairouan region has the highest NKH incidence rate, worldwide. However, due to lack of confirmatory enzymatic and genetic tests, NKH diagnosis was based on first-line biochemical tests. Characterization of causal mutations is needed for accurate diagnosis and prenatal diagnosis of this devastating life-threatening disease.

Homozygous Novel Variants in the Glycine Decarboxylase Gene Associated with Nonketotic Hyperglycinemia in a Distinct Population

“…12 In Tunisia, 69 patients were diagnosed with NKH over a 20-year period. 16 The molecular characteristics of most of these patients were not studied. This is the first report to characterize the clinical and mutation pattern among this Middle Eastern ethnic population.…”

“…12 In Tunisia, 69 patients were diagnosed with NKH over a 20-year period. 16 The molecular characteristics of most of these patients were not studied.…”

“…10 Among Arabs, there were some individual reports, but the exact incidence of NKH among them has not been studied. [11][12][13][14][15][16] Clinically, NKH is classified as neonatal, infantile, and lateonset, based on the age of onset and severity of the disease. 1 The diagnosis depends on the findings of hyperglycinemia and elevated cerebrospinal fluid (CSF) glycine level in the absence of an organic acid disorder.…”

“…10 Among Arabs, there were some individual reports, but the exact incidence of NKH among them has not been studied. 11 12 13 14 15 16…”

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

“…Electroencephalography (EEG) is used to assess brain and seizure activity in NKH. The usual patterns seen are burst-suppression, hypsarrhythmia, and multifocal epileptiform activity [4,5]. Epilepsy of infancy with migrating focal seizures (EIMFS) in NKH has never been described in the literature.…”