Acts Pzdiatr S c m d 68: 629-634, 1979
CASE REPORT
NONKETOTIC HYPERGLYCINEMIA Clinicul, Biochernicul und Therapeutic Aspects S. K g L V R A A . N . J. B R A N D T and E . CHRISTENSEN
of Clinicul Genetics, Department of Puediutrics und the Department qf' Neonatology, University qf Copenhagen, RigJliospitulet, Denmurk
Frorri the Section
ABSTRACT. Kelvraa, S., Brandt, N+J., and Christensen, E. (Section of Clinical Genetics, Department of Paediatrics and Department of Neonatology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark). Nonketotic hyperglycinemia. Clinical, biochemical and therapeutic aspects. Acta Paediatr Scand, 68: 629, 1979.-A patient exhibiting progressive cerebral depression from the first days of life is described. The diagnosis of nonketotic hyperglycinernia was established on the typical clinical presentation, elevated glycine concentrations in body fluids and diminished glycine cleavage activity in liver tissue. A series of therap ratic trials, including strychnine treatment, was tried on this patient without apparent effect on the clinical course.
KEY WORDS: Nonketotic hyperglycinemia, glycine cleavage activity, strychnine treatment
Hyperglycinemia was first described as a syndrome by Childs et al. (3). It is now possible, on clinical and biochemical criteria, to differentiate this syndrome into several distinct entities, namely the disease presented in this paper, nonketotic hyperglycinemia, the ketotic forms, propionic acidemia ( l), methylrnalonic acidernia (10) and @-ketothiolase deficiency (5) and the newly published Dglyceric acidemia (2, 7). Nonketotic hyperglycinemia is clinically characterized by neonatal onset of hypotonia, lethargy and seizures, followed by severe mental retardation. Biochemically it is characterized by elevated glycine concentrations in blood, urine and spinal fluid and diminished activity of the glycine cleavage system in liver and brain (12). Many therapeutic attempts have been tried to relieve the symptoms of nonketotic hyperglycinemia. Most of these have aimed at lowering the glycine concentration in serum either by diet, by administering compounds that form easily excretable conjugates with 41-792873
glycine, or by donkting (?,,-fragments (1 1 ) . Recently a more direct attempt to lower spinal fluid glycine has been tried by Krieger et al. (6), namely insertion of a ventricular shunt. Strychnine treatment h i s also been tried (4). This is based on the observation that the effect of glycine on synaptic transmission is contrary to the effect of strychnine, especially on spinal centres (15). The present communication describes the clinical and biochemical presentation of a case of nonketotic hyperglycinemia, together with the therapeutic attempts that we have performed. CASE REPORT The patient, a boy, is the first child of nonconsanguineous parents. T h e mother has in a previous marriage given birth to a normal boy. Pregnancy and delivery was uneventful. Birth weight 3 600 g. The child appeared normal at birth, but from the second day of life h e became increasingly listless. From the fifth day, insufficient respiration occurred which caused the patient to be transferred to the University Hospital. Examination on admission revealed a severely hypotonic child with no spontaneous movements and n o reactions to stimuli. Artificial
630
S . Kalvraa et a / .
Table 1. Quunfitutive determination of'serum und urine amino ctcids Serum (pmol/l) Patient Aspartic acid Threonine Serine Aspargine Glutamic acid/glutamine Proline Glycine Alanine Valine Cyst i ne Methionine Isoleucine Leucine Tyrosine Phenylalanine Ornit hine Lysine Histidine Arginine "
91 I49 435 69 497 246 1 226 387 217 31 29 85 155
87 54 146 166 97 88
Urine (pmo1/24 hrs)
Range in controls''
Patient
25- 72 69-125 103-2 12 37- 51 309-422 1Is233 160-282 272-375 123-206 28- 38 12- 18 30- 57 64- 104 37- 52 35- 54 62- 92 114-201 58- 88 61-129
19 47 102 59 56 Trace 4 894 80 5 9 Trace Trace Trace 29 8 Trace 30 21 1 4
Range in controls" 33-181 4-125
5-24 1 5- I08 46277 Trace 166-495 45-23 1 11- 22 Trace-I I Trace- 1 2 T rd c e-9 Trace- 19 Trace-7 1 Trace-56 T rdc e-79 19- 75 I 17-686 Trace-10
4 children 1-6 years old (2). 8 children 1-6 years old (2). Trace
CASE REPORT
NONKETOTIC HYPERGLYCINEMIA Clinicul, Biochernicul und Therapeutic Aspects S. K g L V R A A . N . J. B R A N D T and E . CHRISTENSEN
of Clinicul Genetics, Department of Puediutrics und the Department qf' Neonatology, University qf Copenhagen, RigJliospitulet, Denmurk
Frorri the Section
ABSTRACT. Kelvraa, S., Brandt, N+J., and Christensen, E. (Section of Clinical Genetics, Department of Paediatrics and Department of Neonatology, University of Copenhagen, Rigshospitalet, Copenhagen, Denmark). Nonketotic hyperglycinemia. Clinical, biochemical and therapeutic aspects. Acta Paediatr Scand, 68: 629, 1979.-A patient exhibiting progressive cerebral depression from the first days of life is described. The diagnosis of nonketotic hyperglycinernia was established on the typical clinical presentation, elevated glycine concentrations in body fluids and diminished glycine cleavage activity in liver tissue. A series of therap ratic trials, including strychnine treatment, was tried on this patient without apparent effect on the clinical course.
KEY WORDS: Nonketotic hyperglycinemia, glycine cleavage activity, strychnine treatment
Hyperglycinemia was first described as a syndrome by Childs et al. (3). It is now possible, on clinical and biochemical criteria, to differentiate this syndrome into several distinct entities, namely the disease presented in this paper, nonketotic hyperglycinemia, the ketotic forms, propionic acidemia ( l), methylrnalonic acidernia (10) and @-ketothiolase deficiency (5) and the newly published Dglyceric acidemia (2, 7). Nonketotic hyperglycinemia is clinically characterized by neonatal onset of hypotonia, lethargy and seizures, followed by severe mental retardation. Biochemically it is characterized by elevated glycine concentrations in blood, urine and spinal fluid and diminished activity of the glycine cleavage system in liver and brain (12). Many therapeutic attempts have been tried to relieve the symptoms of nonketotic hyperglycinemia. Most of these have aimed at lowering the glycine concentration in serum either by diet, by administering compounds that form easily excretable conjugates with 41-792873
glycine, or by donkting (?,,-fragments (1 1 ) . Recently a more direct attempt to lower spinal fluid glycine has been tried by Krieger et al. (6), namely insertion of a ventricular shunt. Strychnine treatment h i s also been tried (4). This is based on the observation that the effect of glycine on synaptic transmission is contrary to the effect of strychnine, especially on spinal centres (15). The present communication describes the clinical and biochemical presentation of a case of nonketotic hyperglycinemia, together with the therapeutic attempts that we have performed. CASE REPORT The patient, a boy, is the first child of nonconsanguineous parents. T h e mother has in a previous marriage given birth to a normal boy. Pregnancy and delivery was uneventful. Birth weight 3 600 g. The child appeared normal at birth, but from the second day of life h e became increasingly listless. From the fifth day, insufficient respiration occurred which caused the patient to be transferred to the University Hospital. Examination on admission revealed a severely hypotonic child with no spontaneous movements and n o reactions to stimuli. Artificial
630
S . Kalvraa et a / .
Table 1. Quunfitutive determination of'serum und urine amino ctcids Serum (pmol/l) Patient Aspartic acid Threonine Serine Aspargine Glutamic acid/glutamine Proline Glycine Alanine Valine Cyst i ne Methionine Isoleucine Leucine Tyrosine Phenylalanine Ornit hine Lysine Histidine Arginine "
91 I49 435 69 497 246 1 226 387 217 31 29 85 155
87 54 146 166 97 88
Urine (pmo1/24 hrs)
Range in controls''
Patient
25- 72 69-125 103-2 12 37- 51 309-422 1Is233 160-282 272-375 123-206 28- 38 12- 18 30- 57 64- 104 37- 52 35- 54 62- 92 114-201 58- 88 61-129
19 47 102 59 56 Trace 4 894 80 5 9 Trace Trace Trace 29 8 Trace 30 21 1 4
Range in controls" 33-181 4-125
5-24 1 5- I08 46277 Trace 166-495 45-23 1 11- 22 Trace-I I Trace- 1 2 T rd c e-9 Trace- 19 Trace-7 1 Trace-56 T rdc e-79 19- 75 I 17-686 Trace-10
4 children 1-6 years old (2). 8 children 1-6 years old (2). Trace
