My son Gage

My 5 year old son remains undiagnosed.  He was born full-term after an uneventful pregnancy.  An emergency c-section was performed due to a drop in heart rate, but there were no further complications except poor feeding.  His Apgar scores were 7 and 8.  His birth weight, length, and head circumference were 6 lbs. 14 oz., 21 inches, and 34 cm, respectively. 

 

At 2 months of age, it was apparent that he couldn't see.  He also had unusual eye movements, such as his eyes rolling down and staying fixed in that position for periods of time.  We took him to the pediatrician, who suspected seizure activity.  We were sent to the local children's hospital, where a 3 day video EEG was performed and seizure activity was documented; however, the eye movements did not correlate with the seizure activity.  I will not try to explain the EEG pattern in detail, as I know I cannot do so properly.  Roughly, the background is extremely chaotic and there are very few periods of normal activity.  We have never seen anything that we are certain is a clinical seizure.  Even without outward manifestations, the neurologist felt it was appropriate to treat based on the EEG since it is so ugly.  Current meds are Keppra and Lamictal, although they have not had much effect on normalizing the EEG.

 

The MRI shows a cerebellar vermis which is about half of normal size.  We have been told that the cerebellum overall is small, although this has not been officially noted in the MRI reports.  There is no "molar tooth sign" as in Joubert Syndrome.  The MRI does not seem to match the severity of the delay.  It is assumed that the proper connections in the brain are not being made.

 

My son has severe hypotonia and cannot sit up or hold his head up.  He can roll over.  He does not have much muscle control, but can manage to bring his right hand to his mouth to chew on it.  He does not hold or play with toys.  He makes noises, but no recognizable vowel or consonant sounds.  He does not understand spoken language as far as we can tell.  We are not sure if he recognizes us.  He can see bright light and will track once in a great while, but is blind for all practical purposes.  Cortical visual impairment has been given as a diagnosis, as there seems to be no other explanation.  An electroretinagram was normal. 

 

He has dysphagia (can't swallow properly and aspirates on all consistencies) and must be tube fed.  A Nissen fundoplication was done to alleviate severe reflux. 

 

He had an odd skin biopsy at 5 months that no one has been able to explain.  I don't know if it is relevant, but I thought I would throw it in just in case.  The biopsy report states "Psoriasiform hyperplasia, absence of the granular cell layer and overlying parakeratosis are all features of psoriasis.  The spongiosis would be unusual for psoriasis; however it is reminiscent of the changes seen in glucagonoma syndrome.  Is the patient on IV glucagon?  Additionally, there are interesting cytopath changes in the perieccrine fat (best on level 2).  I am not aware of any associated metabolic disorder with these changes.  I have examined a section under fluorescent microscopy and find no evidence of autofluorescent deposits as seen in some metabolic disorders."

 

With the exception of ear infections, he has been very healthy and does not get sick often.  His condition seems stable, rather than deteriorating.  His demeanor is generally happy.  He has outbursts of laughter for no apparent reason.  He did have a very slight improvement in head control and alertness/awareness with the introduction of CoQ10.  He is average height and weight for his age -  42 inches and 38 pounds at age 5.

 

Other physical characteristics:  microcephaly, temporal narrowing, tapered fingers, laryngomalacia, low anterior hairline, hyperextensible joints, delayed dental eruption, small teeth, gingival overgrowth, undescended testicle, some hirsutism on back and legs, difficulty with temperature regulation

 

Tests with normal results:

Ammonia

Lactate / Pyruvate {blood & CSF}

CSF Neurotransmitter metabolites: 

     Hydroxyindoleacetic acid

     Homovanillic acid

     3-o-Methlydopa

CSF Amino Acids

Leukocyte enzymes, which ruled out:

     GM1 gangliosidosis

     Beta-mannosidosis

     Tay-Sachs & variants

     Metachromatic leukodystrophy

     Krabbe disease

Acylcarnitine

Urine Oligosaccharide

Carbohydrate Def. Transferrin

Respiratory Chain Complexes I, III, IV on skin fibroblasts

Urine Organic Acids

Succinyl purine (to test for Adenylosuccinate Lyase Deficiency)

Very Long Chain Fatty Acids

No cryptic deletions or translocations of telomere regions

FISH of SNRPN region of chromosome 15

FISH of SMS region of chromosome 17

FISH of LIS1 region of chromosome 17

Microarray (June 2007 & Feb. 2009)

ATR-X

UBE3A (Angelman)

CDKL5 (Atypical Rett)

SNRPN (Angelman)

MECP2 (Rett), one change; likely normal variant; mom has same variation

Mom has normal X inactivation pattern

Hormone & gene testing for Septo Optic Dysplasia

Batten:  One Mutation:  Heterozygous C to T transition in exon 1 of CLN1 gene.  "This alteration predicts amino acid codon change from Pro (CCA) to Ser (TCA) at codon position #16.  Change not previously reported in NCL mutation database."  Note:  PPT enzyme testing was normal

  

As you can see, we have been all over the map with both metabolic disorders and syndromes.  

 

Any suggestions are appreciated! 

 

Susan