Natural history of nonketotic hyperglycinemia in 65 patients

J. E. Hoover-Fong, S. Shah, J. L.K. Van Hove, D. Applegarth, J. Toone, Ada Hamosh

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101 Scopus citations


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 < 1 month for girls (p = 0.02). Mean birth weight and length, occipitofrontal circumference, and gestation duration were normal. Two-thirds of infants were ventilated during the neonatal period; of these, 40% died. Ninety percent had confirmed seizures, 75% during the first month of life. Interestingly, three NKH patients never developed seizures. An abnormal corpus callosum and/or hydrocephalus were associated with especially poor gross motor and speech development. Of 25 patients living ≥ 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.

Original languageEnglish (US)
Pages (from-to)1847-1853
Number of pages7
Issue number10
StatePublished - Nov 23 2004

ASJC Scopus subject areas

  • Clinical Neurology


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