Re: Help..'Menkes Disease'

Posted By peds neuro md on February 24, 1998 at 19:43:59:

In Reply to: Help..'Menkes Disease' posted by Manoj Agnani on January 27, 1998 at 08:38:08:







: Sir/Madam,

My friend's new born (4 months old) son is suffering from a disease,
which has been diagnosed by the doctors in India to be 'Menkes disease'.
But they would not confirm or no two diagnosis of different doctors
would
agree with another.
We would appreciate it very much if some doctor could help us in this
matter.Below
is a brief medical case summary for reference. Any further details
regarding the same can be furnished as need be.

MEDICAL CASE SUMMARY: RAOUL ATTAVAR
Maternal History : Raoul, male child, aged 3 months, residing in Bombay,
is the only child of his non-sanguineous parents. Mother, elderly
primi (35 years) has no h/o previous pregnancies / abortions, underwent
a chorionic villus sampling at 4th month of gestation. This revealed no
abnormality. Maternal history of hypothyroidism 7 years ago, for
which Thyroxin was administered for 3 months. Mother also undertook a 6
month course of Ro-Accutan for acne, 2 years ago.
Birth History : L.S.C.S at 37 weeks due to foetal distress (meconium
stained liquor). Birth weight 2.75 kgs, cried immediately after birth.
Apgar score 8 - 9. Meconium aspirated from stomach soon after birth.
Exaggerated physiological jaundice (15 mg/dl, which lasted almost 2
weeks,
disappeared with exposure to sunlight). Thyroid functions tested, and
found
to be normal.
Clinical History : On November 10th, at age 10 weeks, he presented
with focal twitching of the left supra-orbital area, associated with
drooling.
There also was temporary left facial weakness, with head and eyes turned
towards the left during a convulsion, with cyclical motions of all
extremities.
It was followed by a post ictal daze like state, during which he would
neither cry, nor feed. He is exclusively on breast feeds. These
twitchings
were initially 6 to 8 a day, and in increasing frequency. By November
15th he was getting it every 10 minutes, or so. On examination, his
milestones
were quite delayed. He wasnt holding his head up satisfactorily, was
focusing
only transitionally, and had no social smile. No other abnormalities
detected.
Investigations revealed mild anaemia (Hb - 9.8), normal calcium and
thyroid
hormone levels, mild lacticacidosis, normal T3, T4 and TSH levels,
normal
IgM and IgG torch titres, normal urine aminoacidogram, elevated blood
lactate
(62mg/dl) and pyruvate (1.7 mg/dl) levels, and low copper (15 mg/dl)
and ceruloplasmin (less than 3 mg/dl) levels. An EEG revealed
abnormalities
in the left temporal and parietal areas. MRI studies of the brain, as
well
as MR-Angiography were also done. These were initially reported as
showing suspicious areas, ? infarcts in the left parietal areas, and
tortuous
cerebral vessels (basilar). Other radiologists who have examined both
the
brain and angiography scans, feel they are within normal limits.
Fundoscopic
examinations were also done. One ophthalmologist reported no
abnormality,
whereas another felt that the optic discs and surrounding areas of the
retina were pale. He was administered phenobarbitone orally, and the
convulsions
appeared to have been controlled almost instantaneously. Within an hour
of the first dose, the twitchings were noted to be reducing, both in
frequency
and intensity - and ceased altogether by the very next morning. The
Doctors
treating him are of differing opinion. It was initially thought to be a
biotinidase deficiency, as explained by the elevated blood lactate and
pyruvate levels, but this didnt account for the low copper and
ceruloplasmin
levels. A filter paper blood test has been sent to the USA, results
still
awaited. Also the immediate response to anti-convulsants contradicted
this
diagnosis. At present, one of the doctors is convinced that this is
Menkes
disease (Kinky Hair Syndrome), as explained by the low copper levels and
? tortuous cerebral vessels, but has not explained the elevated lactate
and pyruvate levels. Also, hair analyses shows no abnormality typical
of Menkes. Another doctor feels this could be a mitochondrial disorder.
A filter paper urine test has been sent to the Netherlands to confirm
this.
CSF studies were not done, as it was deemed unnecessary.
Treatment History :
Tab. Biotin (5 mg) 1 B.I.D. : After 8 days of Biotin, blood levels
of lactate (42 mg/dl) and pyruvate (0.73mg/dl) were found decreased.
Results of a repeat EEG taken on the 8th day are still awaited.
Tab. Phenobarbitone (15 mg), 1 at night : No convulsions ever
since first day of administration.
Questions
1] Is this Menkes disease ? If yes, how can one explain the elevated
lactate & pyruvate levels ? If no, what could it be ? Are there any
doctors / researchers anywhere whom we could approach for help ?
2] If it is Menkes, do Copper Histidine injections really help ? Where
are these injections available ? If administered, can it harm the
patient
if this is not Menkes ? What side effects do these have ? Is there any
other therapy ?
2] Can any other investigations be done to arrive at a definate
conclusion
? Where can these be done ? [Note, with limited facilities in India,
more
specific investigations are not available].
Thanking you in advance for your assistance and help. As you can see
it is our desperate plea for help and guidance. We are trying to
approach
as many people as we can, but so far without any success or response.
We hope some doctor/researcher would be able to guide us through this.
Please HELP!

Manoj A.
Dear Manoj,
You pose a very interesting and difficult case.
Menke's disease also known as kinky hair disease is a relatively rare
condition. The main physical characteristics that one sees is the hair
findings which develops over the early course of the disorder. The child
may not have the characteristic hair at birth but usually within the
first year of life would start showing the hair findings. In addition
they also develop seizures early in life as early at the newborn period.
The tortous cerebral blood vessels are also seen in menke's disease as well
as a low copper level. As you have pointed out an abnormal lactate and
pyruvate have have not been reported to be associated with this disease, at
least to the best of my knowledge. Abnormal lactate and pyruvate levels are
usually associated with metabolic and mitochondrial disorders.
I am not sure at what point in time was the lactate and pyruvate studies
done and how severely sick the infant was during the blood drawing.
In answering your questions:
1. Is this menke's disease?
I suggest getting the hair analysis done since the abnormality in menke's
will be present. Repeating the studies of lactate, pyruvate as well as the
urine cooper and serum ceruloplasmin is in order. I would also get urine
organic acids and amino acids repeated. If spinal fluid is obtained
get a csf lactate and pyruvate level as well.
2. Can cooper histidine injections help?
Cooper histidine injection does not help the neurologic aspect of
the disorder but may help the systemic part of it. The answer to your
questions really depends on what aspect of the disease you want to control
3. Side effects?
first you need to document the true decrease in cooper levels. Just
as with any drugs there are side effects. You can refer to the PDR for
the list of possible side effects.
4. Other investigations?
To arrive at a conclusive answer may be diffcult, however one can do enzyme
studies on the liver, and other organs that are affect by menke's disease
to help with the diagnosis
5. Where can these test be done?
they can be done in the US or in england. You will have to call around to
see which centers are capable of doing the test.
Lastly, I recommend that you try to make an appointment to see Dr. Menkes
in California if a foreign trip will be done by the patient.