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Diagnostic tools of metabolic and structural brain disturbances in
neonatal non-ketotic hyperglycinemia
Demet Terek,
1
Ozge Altun Koroglu,
1
Sezgin Gunes,
1
Mehmet Yalaz,
1
Mete Akisu,
1
Sema Kalkan Uçar,
2
Sarenur Gokben,
3
Mahmut Çoker
2
and Nilgün Kultursay
1
Divisions of
1
Neonatology,
2
Metabolism and Nutrition and
3
Neurology, Department of Pediatrics, Ege University Faculty of
Medicine, Bornova, Izmir, Turkey
Abstract Non-ketotic hyperglycinemia (NKH) is a rare autosomal recessive disorder of glycine metabolism. We report a newborn
case of NKH and discuss the effects of this rare disease on brain metabolism and structure together with amplitude-
integrated electroencephalography, cranial magnetic resonance and magnetic resonance spectroscopy findings which are
very rarely reported together so far.
Key words amplitude integrated electroencephalography, glycin encephalopathy, magnetic resonance spectroscopy, metabolic
disorder, newborn.
Non-ketotic hyperglycinemia (NKH) is a rare autosomal reces-
sive disorder affecting glycine metabolism with a reported preva-
lence of 1:60.000–100.000. The biochemical defect is in the
glycine cleavage system which consists of a mitochondrial
enzyme complex. There are four forms of glycine encephalopa-
thy: neonatal; infantile; transient; and late.
1
The enzyme level is
close to zero in the neonatal form which is the most common and
severe form. The clinical manifestations of poor sucking, hypo-
tonicity, lethargy, hiccups and seizures develop within 6 h to 8
days of birth of an otherwise healthy newborn. Acute neurologi-
cal deterioration rapidly progresses to coma and often leads
to death in a short period. If patients survive the ventilator-
dependent period, they will suffer from severe mental and devel-
opmental retardation and seizures.
We report a case of newborn NKH and discuss the effects of
this rare disease on brain metabolism and structure, we also look
at using amplitude-integrated electroencephalography (aEEG),
cranial magnetic resonance imaging (MRI) and magnetic reso-
nance (MR) spectroscopy findings, which have been very rarely
reported together previously.
Case report
A female infant was born at term (39 weeks gestation) with a
birth weight of 3200 g, to a gravida 3 para 0 mother, (second-
degree consanguineous parents had an unremarkable family
history) after a pregnancy complicated with chronic hyperten-
sion. The infants Apgar scores were 7 and 9 at 5 and 10 min,
respectively.
On day 2, the infant was admitted to the neonatal intensive
care unit because of decreased movements, shallow breathing
and poor sucking. The physical findings were hypotonicity, leth-
argy, decreased newborn reflexes and pes equinovarus. The
patient was intubated and mechanical ventilation was initiated
because of respiratory acidosis.
Routine biochemical and hematological tests including blood
glucose and complete blood count were unremarkable. Since
neonatal sepsis could not be ruled out, ampicillin and netilmicin
antibiotherapy was initiated. Blood, cerebrospinal fluid and urine
cultures were negative. On her 4
th
day of life the patient began to
have persistent hiccups and myoclonic seizures unresponsive to
treatment. A continuous burst suppression pattern indicating
severe–moderate brain damage was observed on aEEG (Fig. 1).
Metabolic disorders were investigated because of parental con-
sanguinity, and clinical and aEEG findings. Blood lactate, pyru-
vate and ammonia levels were normal. Initially, conventional
electroencephalography (EEG) showed low-voltage baseline
rhythm. However, a later EEG performed after the onset of
Correspondence: Demet Terek, MD, Ege University Faculty of Medi-
cine, Children’s Hospital, Bornova 35100, Izmir, Turkey. Email:
demet.terek@yahoo.com
Received 14 June 2011; revised 21 December 2011; accepted 26
January 2012.
doi: 10.1111/j.1442-200X.2012.03591.x
Refeeding syndrome in a SGA micro-preemie 717
© 2012 The Authors
Pediatrics International © 2012 Japan Pediatric Society