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Nonketotic hyperglycinemia. A genetic study of 13 Finnish families
Insights
Nonketotic hyperglycinemia (NKH) affects 1 in 55,000 Finnish newborns, with higher incidence in northern Finland. Genetic factors likely contribute to this rare metabolic disorder.
Area of Science:
- Medical Genetics
- Metabolic Disorders
- Pediatrics
Background:
- Nonketotic hyperglycinemia (NKH) is a rare genetic metabolic disorder.
- Previous studies have indicated a potential genetic predisposition in certain populations.
Purpose of the Study:
- To determine the incidence and geographical distribution of nonketotic hyperglycinemia (NKH) in Finland.
- To investigate the inheritance pattern and carrier state of NKH.
Main Methods:
- Epidemiological analysis of diagnosed NKH cases in Finland (1964-1977).
- Analysis of birthplaces of patients and grandparents to assess geographical clustering.
- Statistical analysis to determine the mode of inheritance (Apert's a priori method).
- Biochemical analysis of plasma and urinary glycine levels in patients, parents, and siblings.
Main Results:
- Identified 19 NKH cases from 13 families in Finland, yielding an overall incidence of 1:55,000 newborns.
- Observed a significantly higher incidence (1:12,000) in northern Finland, with geographical clustering of ancestral origins.
- Autosomal recessive inheritance is suggested by a sibling recurrence risk of 0.288.
- Elevated plasma and urinary glycine levels were found in parents and some healthy siblings, indicating a carrier state with a minor metabolic defect.
Conclusions:
- NKH exhibits a distinct geographical distribution in Finland, suggesting founder effects or genetic enrichment in the northern region.
- The findings strongly support an autosomal recessive inheritance pattern for NKH.
- Heterozygote carriers for NKH may display subtle metabolic alterations, but definitive carrier diagnosis is challenging due to overlapping biochemical values.
Abstract:
In Finland, 19 children, born 1964--1977, from 13 families, have been diagnosed as suffering from nonketotic hyperglycinemia (NKH). This gives an incidence for NKH in the Finnish population of 1:55,000 newborns. The majority of these children were born in the northern part of the country, where the incidence is 1:12,000. The geographical distribution of the birth-places of the grandparents also seems to point towards an enrichment of the gene in northern Finland. An autosomal recessive mode of inheritance for this disease seems probable, since the corrected proportion of affected siblings (Apert's a priori method) is 0.288. Abnormally high plasma glycine concentration and elevated glycine urinary excretion in the parents of the NKH-children suggest the existence of a minor metabolic defect in heterozygotes of this disease. Some of the healthy siblings of the NKH-patients also show similary elevated levels. However, a definite diagnosis of the NKH-heterozygote state cannot easily be made on the basis of these laboratory findings, as the levels in some individuals are very close to, or even overlap corresponding values in a normal material.