This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Hereditary fructose intolerance
This is due to a deficiency of fructaldolase B and can be demonstrated in liver and intestine biopsy samples. Symptoms of sweating, vomiting and trembling are precipitated by feeding sucrose. There is hypoglycaemia, fructosaemia, fructosuria, hyperuricaemia and aminoaciduria. If the condition is not recognised and exposure to fructose continues, then jaundice, hepatomegaly, oedema, ascites, haemorrhage and eventually death will follow. Many of the liver function tests are abnormal.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Maple syrup urine disease
This is due to a deficiency of branched chain alpha-ketoacid decarboxylase. There is hypertonicity alternating with flaccidity, opisthotonus and nystagmus, convulsions and often mental retardation. There are branched chain amino acids and keto acids in the urine.
minoaciduria. If the condition is not recognised and exposure to fructose continues, then jaundice, hepatomegaly, oedema, ascites, haemorrhage and eventually death will follow. Many of the liver function tests are abnormal.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Lesch-Nyhan syndrome
This presents in affected males (it is an X-linked disorder) with delayed motor development in the first few months leading to choreoathetosis, spasticity and a bizarre urge to self-mutilation such as biting off finger tips.
Due to a deficiency of hypoxanthine-guanine-phosphoribosyl transferase (HGPRT), the striking biochemical feature is a gross hyperuricaemia. The diagnosis may be confirmed by demonstrating the enzyme deficiency in cell extracts.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Tay-Sachs' disease
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Booth-Danks syndrome
This is characterized by rectopthmus and a general photophobia in the presence of computer monitors. There is an irrational fear of rodents, most noticably mice. There is often a neurosis connected with particularly obscure metabolic diseases. Carbohydrate metabolism is normal, the glucose tolerance test etc. etc. ...how are you feeling now?
kenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Juvenile-onset diabetes mellitus
This presents over a period of a few weeks with thirst, polyuria and rapid weight loss. There is glycosuria and progressive hyperglycaemia and ketoacidosis. Untreated the condition will rapidly progress with metabolic acidosis, hyperventilation, vomiting, abdominal pain and dehydration leading to circulatory collapse, coma and death.
In such cases, diagnosis is made on the basis of unequivocal hyperglycaemia and ketoacidosis. The glucose tolerance test is unnecessary.
Glucose tolerance: hypoglycaemia at beginning and end with
glucose concentration rising to abnormally high level.
Marked decrease in blood lactate.
Glycerol challenge: no change in blood glucose concentration,
increase in blood lactate concentration.
Glucagon challenge: decrease in blood glucose concentration.
Galactose infusion: decrease in blood glucose concentration.
Fructose infusion: decrease in blood glucose concentration..
Provocative tests
Graph
4pack
tgraph
there
buttonUp
rightButtonUp
buttonUp
rightButtonUp
Peter W.
Patient:
After fasting, glucose (1.75 g/kg body weight)
was given orally at
time zero.
Details
"Provocative"
buttonUp
buttonUp
Provocative
see_over
see over...
Diagnosis3
Diagnoses
B"OK"
buttonDoubleClick
buttonDoubleClick
buttonUp
Juvenile-onset diabetes mellitus
von Gierke's disease
Glycogen storage disease type 1b
Pompe's disease
Galactosaemia
Hereditary fructose intolerance
Maple syrup urine disease
Lesch-Nyhan syndrome
Tay-Sachs' disease
Booth-Danks syndrome
"Diagnosis"
B"OK"
buttonUp
buttonUp
Diagnosis
buttonUp
Diagnosis
Cancel
4lastPage
buttonUp
buttonUp
lastPage
Cancel
:PHYSSIZE
Tay-Sachs' disease
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Glycogen storage disease type 1b
This is clinically very similar to von Gierke's disease (q.v.). Glucose 6-phosphatase is present at normal levels of activity, but it shows abnormal latency, i.e. full activity is only seen after disrupting membrane structures with freezing and thawing or by treatment with detergent. The defect is in the glucose 6-phosphate translocase T1, which transports glucose 6-phosphate from the cytoplasm into the lumen of the endoplasmic reticulum. These patients often have a neutropaenia.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Pompe's disease
This is due to an absence of the lysosomal enzyme alpha-1,4-glucosidase which can be demonstrated in cultured fibroblasts. It presents in the first few months of life, with marked hypotonia and cardiomegaly, hepatomegaly not becoming marked until the inevitable heart failure becomes severe.
There is accumulation of glycogen, an abnormal response to glucagon but no hypoglycaemia. As yet there is no effective treatment and death is inevitable, usually within the first twelve months.
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
Galactosaemia
This is due to a deficiency of galactose 1-phosphate uridyl transferase which can be detected in cultured fibroblasts. Normal at birth, symtoms start to appear as early as the second week with weight loss, jaundice, vomiting and hepatomegaly. After a few weeks cataracts develop. Unless the condition is quickly recognised death is inevitable and unless treatment (the substitution of a galactose (milk) free diet) is started in the first week of life a degree of mental subnormality appears inevitable.
On examination the child is apyrexial, pale, clammy and irritable with a pulse rate of 110 per minute. There is no jaundice or anaemia clinically and the mucous membranes are a good colour with no sign of central cyanosis. He is rather small for his age (height below the third percentile), with poor developmental milestones, but does indeed have a very chubby appearance with a very round face. The throat and both tympanic membranes are of normal appearance. On abdominal examination there is gross hepatomegaly, the liver extending three finger breadths below the costal margin. There are no abnormal findings in the respiratory or cardiovascular systems with no evidence of heart failure and neurological examination is normal. Examination of the optic fundi was not easy, but there are no gross abnormalities.
Examination
Examination_details
:PHYSSIZE
Note the chubby face and distended abdomen
Patient:
Peter W.
Details
"Examination_done"
buttonUp
buttonUp
Examination_done
Diagnosis2
Diagnoses
B"OK"
buttonDoubleClick
buttonDoubleClick
buttonUp
Juvenile-onset diabetes mellitus
von Gierke's disease
Glycogen storage disease type 1b
Pompe's disease
Galactosaemia
Hereditary fructose intolerance
Maple syrup urine disease
Lesch-Nyhan syndrome
Tay-Sachs' disease
Booth-Danks syndrome
"Diagnosis"
B"OK"
buttonUp
buttonUp
Diagnosis
buttonUp
Diagnosis
Cancel
4lastPage
buttonUp
buttonUp
lastPage
Cancel
:PHYSSIZE
Tay-Sachs' disease
This usually presents at 4-6 months of age with progressive neurological symptoms. Delay in psychomotor development, irritability, spasticity, weakness and muscle wasting lead to loss of vision, deafness and decerebrate rigidity. Death occurs usually by three years. It is inherited as an autosomal recessive character and is 100 times commoner in Ashkenazi Jews than in the general population. Due to a deficiency of beta-N-acetyl hexosaminidase.
erance test is unnecessary.
utropaenia.s inevitable.
Diagnosis1
von Gierke's disease
This is glycogen storage disease type 1a. It is characterized by an absence of glucose 6-phosphatase in biopsies of liver, intestine or in platelets. There is hepatomegaly, hyperuricaemia, hypoglycaemia and hyperlipidaemia, but no aminoaciduria or ketosis. The glucose tolerance test shows an abnormal rise in blood glucose concentration with hypoglycaemia at the beginning and end. There is an abnormal response to glucagon with an increase in blood lactate but not glucose.
Dismiss
"Diagnosis"
keyEnter
buttonUp
keyChar
buttonUp
Diagnosis
keyChar
Diagnosis
Diagnosed1
Diagnosis:
von Gierke's Disease (Glycogen Storage Disease Type 1a).
Treatment:
The main problem with these patients is the fasting hypoglycaemia which may cause convulsions. This can be controlled by frequent feeding day and night using a nasogastric tube if necessary. These patients often present in their teens with gout and this can be controlled with allopurinol. There is often a platelet dysfunction that can cause bleeding disorders.
see over...
Diagnosis
Diagnosed1
Diagnosis4
Diagnosed2
You should have noticed the following about this patient:
The fasting blood glucose concentration was low, while the concentrations of lactate, urate, cholesterol, triglycerides and fatty acids were all raised. There was no glucose in the urine nor were there any ketones. (The early report of ketones in the urine of patients with von Gierke's disease is now know to be incorrect.) The urea and electrolytes showed an acidosis with decreased bicarbonate and increased anion gap. Chromatography of the urine showed no hyperaminoaciduria. The provocative tests all gave abnormal results, although you will not have been able to do all of them without harming the patient in this case. The definitive test is, of course, the liver biopsy but in view of the risk and discomfort, it should only be done when other tests indicate that it would be worthwhile.
see over...
Further comments
Diagnosed3
The haematology report showed that although the platelet count was normal, the bleeding time was longer than usual. Radiology simply confirmed the hepatomegaly. ECG showed that there was no cardiac problem. EEG and lumbar puncture added nothing and simply wasted resources. You can now go back and do any of the tests that you missed.
Before you finish, answer these questions;
1 - Why does a build-up of glucose 6-phosphate lead to the
deposition of large quantities of glycogen.
2 - Apart from hydrolysis to glucose, what are the other
metabolic fates of glucose 6-phosphate?
3 - Explain why each of the provocative tests gave abnormal
results. see over...
Further comments
Diagnosed4
4 - The active site of glucose 6-phosphatase is located on the
non-cytoplasmic side of the endoplasmic reticulum membrane.
How does glucose 6-phosphate reach the active site from the
cytoplasm and how are the products returned.
5 - What would be the consequence of the failure of any of the
components of the system that you describe in answer to 4?
This five month old caucasian infant was brought to the receiving room this afternoon following a convulsion. His mother volunteers the information that he has been prone to attacks of irritability, sweating and pallor, relieved by feeding, since soon after birth. This afternoon she was out shopping when these symptoms developed. Before she was able to feed him he had a prolonged convulsion. He was conscious on arrival and has been fed. I feel that he should be admitted for observation and investigation.Q
4diagnosed, lastPage
"Admission"
"Biopsy"
"Diagnosed4"
"Diagnosis"
"About"
"Diagnosed1"
uttonUp
rightButtonUp
buttonUp
rightButtonUp
Admission
Biopsy
Diagnosed4
Diagnosis
About
diagnosed
lastPage
buttonUp
Biopsy
Admission
Diagnosed1
Diagnosed4
Admission
Diagnosis
About
diagnosed
lastPage
Admission
Plain
History_done
userAction
4score,
,diagnosed
e"History"
"Author"
"Reader"
"History_done"
setup
userAction
setup
userAction
History
Author
Reader
History_done
score
history
diagnosed
setup
History
Author
Reader
History
history
The child was a full term normal delivery to a healthy twenty six year old woman. This was her third pregnancy and there were no complications. The two previous pregnancies were also normal but the first child died at three weeks following a convulsion. The other child is a normal, healthy three year old. Neither parent has any history of ill health or convulsion in childhood and there is no relevant family history.
In the first few weeks, his mother noticed that he became pale, sweaty and irritable before feeds, particularly if the feed was delayed. As time went on, these symptoms led her to give him frequent feeds and it was to this that she attributed his rather fat appearance and round face. Today the feed was delayed and he had a generalized convulsion lasting several minutes.
History
Examination_done
On examination the child is apyrexial, pale, clammy and irritable with a pulse rate of 110 per minute. There is no jaundice or anaemia clinically and the mucous membranes are a good colour with no sign of central cyanosis. He is rather small for his age (height below the third percentile), with poor developmental milestones, but does indeed have a very chubby appearance with a very round face. The throat and both tympanic membranes are of normal appearance. On abdominal examination there is gross hepatomegaly, the liver extending three finger breadths below the costal margin. There are no abnormal findings in the respiratory or cardiovascular systems with no evidence of heart failure and neurological examination is normal. Examination of the optic fundi was not easy, but there are no gross abnormalities.
(.txt)