About
NKH
About
NKH
To learn more about NKH, choose one or more of the options below.
Nonketotic Hyperglycinemia is an inherritted metabolic disorder. Patients suffering from this disorder have elevated level of glycine, a basic amino acid, in blood, cerebrospinal fluid (CSF), and urine. The diagnostic characteristic is the elevated ratio of glycine in CSF/blood. Some patients died in the newborn period after a course characterized by lethargy, weak cry, generalized hypotonia, absent reflexes, and periodic myoclonic jerks. Survivors are subject to various degrees of mental retardation.
NKH has a very wide spectrum of severity. There are two way of classifications: one is based on clinical manifestations, and the other is based on underlying enzymatic causes.
The clinical categorization of NKH falls into four broad groups: classical or neonatal NKH, infantile NKH, late-onset NKH, and the rare transient NKH. Most NKH children are of classical group.
The enzymatic categorization divides NKH into four types, based on the location of deficient sub-enzymes in the glycine cleavage system (GCS), which is the large and complex enzyme that is supposed to gets rid of excessive glycine.
Progress has been made during the past decade for a better treatment of NKH. Unfortunately, due partly to the disorder's heterogenuity, no absolute cure has yet been found. Sodium Benzoate (SB) has long been used to reduce the excessive glycine in both plasma and CSF, and can results in controlled or reduced seizures and increased alertness. Recent trials of higher doses of sodium benzoate succeeded in normalization of plasma glycine and substantial reduction in CSF. In contrast to earlier reservation among medical researchers upon the role of sodium benzoate in promoting mental development, the experiences among many of our parent members seem to indicate the benefit of sodium benzoate. (Exceptions do occur, though). This seems to be true especially when the children start taking sodium benzoate at high enough dose early in life (within the first years of life).
The most serious side effect from SB is its irritation on stomach due to its acidity. At high dose, some children developed inflammations in stomach, duodenum, esophagus. Few suffer from recurrent heartburn and fail to gain weight. Protective medications have been prescibed. These include antacids, H2-blocker (e.g. Zantag), protein pumb inhibitor, and sucralfate. These protective medications work differently, and it is a matter of trial and error to find the most suitable strategy for each child. The SB's side effect is apparently dose dependent. Many medical articles confirm that a dose of 250 mg/kg/day is well tolerated. Some NKH children of our network can take as much as 500-600 mg/kg/day without too much stomach irritation and without any protective medications. Consequently, if a child can poorly tolerate the proper dose, it might be wise to investigate into other possible complication. The author's personal experience has found that a problem of delayed gastric emptying greatly reduces the tolerability, as the sodium benzoate stays in the stomach for too long. Correcting this problem results in much better tolerance of sodium benzoate.
Dextromethorphan (DM or DXM)�is another principal medication added recently to the treatment of NKH children. It has been found in animal model to prevent neuron death resulting from the brain being exposed to high glycine. Some researches also indicate that DM prevents or reduces seizures. (Personal experience by the author of this webpage seems to confirm both the seizure prevention and the development promotion of DM). However, DM can have relatively strong side effects, especially after long term and regular use. It can cause irritability, involuntary movements, refusal to eat, troubled sleeping and breathing suppression. The side effects are different from child to child, and seem to be caused by substantial difference in the body's metabolism of dextromethorphan into dextrophan. The optimal dose (or practical dose) for each child is therefore quite different. To learn more about DM, there is a FAQ (frequently Asked Questions) on DM which can be found at William E. White's Dextromethorphan FAQ.
Since NKH is an autosomal inherited inborn disorder, the chance that parents who are both carriers of this disease (those who already have or had affected child) will have another NKH child is one in four, a normal child is also one in four, and two in four will be carriers. The question is how we can know during pregnancy if the child is affected for not. Fortunately, prenatal diagnosis has been available for quite some time. The medical literature on this diagnosis come from both Japan and North America. One of the center that has done most prenatal diagnosis is the Biomedical Diseases Laboratory of the Division of Biomedical Diseases at the University of British Columbia, Vancouver, Canada. Dr. Derek Applegarth has done twelve prenatal diagnoses so far (as of January 1997). Out of these twelve pregnancies, the diagnosis can be made with accuracy (that the child was either affected or normal) in nine of them. The result on the other three pregnancies were inconclusive (in "grey area"), as the GCS enzyme activities were detected but were not in normal range. That means the child can be anything from normal to mildly affected (atypical NKH), or even classical NKH.
We have to interpret these number carefully. The good thing is that if the data is strong enough, the diagnosis has been always right so far. And that is nine out of twelve, not a bad number. However, the risk is still there because of the possibility like the three inconclusive cases. It is not possible to make prediction on those cases and the parents still have to make a very tough decision, either to keep or to abort the pregnancy. Also, the total number of twelve diagnoses that has been done is still too small to say that, statistically, these "inconclusive" diagnoses are less likely to happen than the conclusive ones. We can only hope that even more accurate diagnosis will be developed very soon.