Natural history of nonketotic hyperglycinemia in 65 patients


Natural history of nonketotic hyperglycinemia in 65 patients


Hoover-Fong JE; Shah S; Van Hove JL; Applegarth D; Toone J; Hamosh A






Child; Female; Humans; infant; Male; Pregnancy; Questionnaires; Disease Progression; Respiration; Survival Analysis; Sex Factors; Registries; adolescent; Preschool; infant; Newborn; AIM; IM; retrospective studies; Age of Onset; Health Surveys; Artificial; Seizures/et [Etiology]; Anticonvulsants/tu [Therapeutic Use]; Apnea/et [Etiology]; Apnea/th [Therapy]; Corpus Callosum/ab [Abnormalities]; Glycine/bl [Blood]; Glycine/cf [Cerebrospinal Fluid]; Hydrocephalus/ep [Epidemiology]; Hydrocephalus/et [Etiology]; Hyperglycinemia; Juvenile/dt [Drug Therapy]; Juvenile/ep [Epidemiology]; Juvenile/et [Etiology]; Myoclonic Epilepsy; Nonketotic/co [Complications]; Nonketotic/ep [Epidemiology]; Nonketotic/me [Metabolism]; Nonketotic/mo [Mortality]; Nystagmus; Pathologic/ep [Epidemiology]; Pathologic/et [Etiology]; Pregnancy Complications/ep [Epidemiology]; Psychomotor Disorders/ep [Epidemiology]; Psychomotor Disorders/et [Etiology]; Seizures/dt [Drug Therapy]; Seizures/ep [Epidemiology]


BACKGROUND: Glycine encephalopathy, also known as nonketotic hyperglycinemia (NKH), is an autosomal recessive disorder caused by a defect in the glycine cleavage system. NKH is classically associated with neonatal apnea, lethargy, hypotonia, and seizures, followed by severe psychomotor retardation in those who survive. METHODS: To determine the natural history of NKH, the authors mailed a 44-question survey to 170 households in the International NKH Family Network. RESULTS: Data for 65 patients (36 boys, 29 girls) were collected from 58 families. One-third of the subjects died; 8 girls died during the neonatal period, and 14 patients died thereafter (2 girls, 12 boys). Median age of death for boys was 2.6 years vs or =3 years, 10 were able to walk and say/sign words; all were boys. In six families with more than one affected child, disease course and mortality were similar within each family. CONCLUSIONS: This study reveals a striking and unexpected gender difference in mortality and developmental progress. Of the two-thirds of nonketotic hyperglycinemia patients surviving the newborn period, up to 20% (mostly boys) may learn to walk and communicate by saying or signing words.


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Hoover-Fong JE; Shah S; Van Hove JL; Applegarth D; Toone J; Hamosh A, “Natural history of nonketotic hyperglycinemia in 65 patients,” Pediatric Palliative Care Library, accessed December 2, 2023,