July 23, 2001

Dear Dr. Horam:

I had the opportunity to see your patient, Aschdon Birkle, during his visit to the Muscle Clinic at The Children’s Hospital on June 7, 2001. We had previously spoken regarding Aschdon and your concerns regarding some abnormal metabolic studies that you had obtained at an earlier date. Aschdon is a two-year-old child with a history of failure to thrive, developmental delay and significant hypotonia for which he was being evaluated in the Muscle Clinic. As we discussed, I saw him briefly during his visit here to save the family an additional trip and to further coordinate metabolic studies. This letter will briefly review Aschdon’s history as described by his mother and review his physical examination and my thoughts and recommendations.

Birth History: Aschdon was born at 32 weeks gestation weighing 3 pounds 13.5 ounces and was 15 inches in length with a head circumference of 29.2 cm. He initially required some oxygen, but was on room air within 24 hours. He also received a brief course of antibiotics. He was discharged to home on day eight of life.

Past Medical History: Aschdon has a history of frequent otitis media occurring approximately monthly. He also has a history of frequent upper respiratory infections and bronchitis. He ahs been hospitalized twice for pneumonia and was recently diagnosed with strep throat. He is not felt to have underlying lung disease and his mother reported that a previously obtained chest X-ray was normal. There has been long-standing concern regarding his growth. Review of his growth records which you provided show that in the recent past he has been tracking along a growth percentile markedly less than the 5th percentile. Presently for an eight and a half month old child, his height is at the 50th percentile for a seventeen and a half month old child, and his head circumference is between the 10th and 25th percentiles for age. His mother described him as a picky eater who has a difficulty with textures. He does not appear to have any food aversions and certainly consumes a wide variety of protein-containing products such as meat and dairy products. His diet is supplemented with Pedisure and has been since approximately eight months of age. If he is feeling well, his mother reported that he cant take three to four cans per day. If he is not feeling well, he takes approximately one can per day.

Developmental History: Aschdon has global developmental delays. Reported milestones include rolling at approximately seven to eight months of age and sitting at approximately eighteen months of age. At this time, he still cannot get into a sitting position on hi own. He does no crawl, scoot, or stand. His vocabulary includes approximately fifty to seventy-five words and three to four two-word phrases. He was evaluated in an outreach clinic on May 7th by Dr. Ed Goldson who suggested a Muscle Clinic evaluation. Aschdon has not had any regression of developmental skills.

Laboratory Studies: Cranial MRI performed on March 20, 2001 was with in normal limits. Thyroid function studies were normal. A comprehensive metabolic panel was normal with the exception of a mildly increased anion gap of 14. CBC was normal with an MCV of 83.2. These laboratory studies were all collected on August 22, 2000. Sweat chloride test, fecal reducing substances and qualitative fecal fat counts were also within normal limits obtained on September 1, 2000. Additional labs obtained on May 7, 2001 include a serum CPK of 246, an ammonia of 39, normal immunoglobulin levels, and normal serum carnitine level. C3 and C4 complement levels were also normal as were serum amino acids. Repeat CBC obtained on May 7, 2001 revealed a hemoglobin of 12 and hematocrit 35.6, both borderline low. His MCV continued to be normal at 88.2 and his platelets were 385. In addition, a urinalysis was unremarkable. Repeat creatine kinase was 120 and urine amino acids had a multiple elevated levels with an interpretation of a “non-specific pattern of elevated amino acids that was not consistent with any known disorder”. Per report, urine organic acids were also ordered, however, I have not seen those results.

Family History: A brief family history was obtained on the day of the clinic visit. Aschdon has one full sibling who is currently three years old and has a possible milk allergy. He also has a maternal half sister who is nearly six years of age and who is noted to be quite small in size, but otherwise healthy and developmentally appropriate. Aschdon’s mother is currently undergoing a rheumatologic work-up due to markedly elevated IgE levels. She also has a history of allergies and asthma, and a history of easy fatigability. She is 5’4’’ tall. Aschdon’s father is reportedly healthy and 6’2’’ tall. Further paternal family history is notable for seizures in a paternal uncle. Further maternal history is notable for a maternal aunt with a history of pulmonic stenosis, another maternal aunt with a history of ADD, and a maternal uncle with a history of chronic bronchitis and dyslexia. Aschdon’s maternal great grandfather was noted to have multiple sclerosis and osteoporosis. There is also a maternal family history of cancer. The ethnicity on both sides of the family is German and on the maternal side also includes American Indian.

Physical Examination: Although I am confident that growth parameters were obtained at the clinic visit in the Muscle Clinic, I failed to obtain them for my records. In general, Aschdon was an alert, relatively cooperative white male child in no acute distress, but quite small for his stated chronological age. HEENT examination was significant for a triangular facies, a small mouth, and relatively straight nose. His lungs were clear to auscultation and his heart had a regular rate and rhythm without murmur. His abdomen was benign. Genitourinary examination revealed descended testicles and circumcised male genitalia. Extremity examination revealed fifth finger clinodactyly bilaterally, very mild two-three toe syndactyly, spoon-shaped toes, long digits, prominent heels, and inability to extend knees to complete 180 degrees. He had quite thin extremities with markedly decreased muscle mass and muscle bulk. Neurologic examination revealed global hypotonia. He was unable to get into a sitting position without assistance, but did not have head lag when pulled into a sitting position. He appeared to be areflexic. Cranial nerves 11-X11 were grossly intact. Skin was clear.

Impression/Recommendations: Aschdon is a two-year old child with significant developmental delays globally, but motor greater than speech, poor growth, and mild dysmorphic features. Upon seeing him and reviewing his laboratory studies, my suspicion of a metabolic disease is quite low. Rather, I have an increases suspicion for an underlying genetic disorder or genetic syndrome. Repeat metabolic studies, however, are indicated to follow-up the abnormal results previously reported. Hence, at the clinic visit, samples were obtained for repeat urine organic acids, urine amino acids, and quantitative serum amino acids. As noted, his overall phenotype is more suggestive of a genetic syndrome or etiology, and hence I also ordered high-resolution chromosome analysis and FISH analsis for a deletion of 22q11. Dr. Julie Parsons and I also felt it was important to order copper and ceruloplasmin levels and she ordered testing for SMA. Follow-up evaluations and visits will be decided once the results of the above laboratory studies are available. It is my understanding that if results are normal, Dr. Parsons may proceed with a muscle biopsy and this does seem like a reasonable course in this child with significant hypotonia, poor muscle bulk and mass, and areflexia.

It was my pleasure to have the opportunity to briefly see Aschdon Birkle in conjunction with his Muscle Clinic visit. I hope my input proves beneficial to this family and to you. I will continue to work with Dr. Parsons and the genetics coordinator for Muscle Clinic regarding follow-up for this patient.

Sincerely,

Janet A. Thomas, MD

Assistant Professor Pediatrics

Director, IMD Clinic

Please be aware that the information in this letter reflects our current level of knowledge in human metabolism and biochemical genetics. Rapid progress in our field consistently produces new understanding about the diagnosis, management and recurrence risk of metabolic disorders. It is important that you periodically seek updated information, especially before any reproductive decisions are made.

Cc: Julie Parsons, MD

Muscle Clinic

Addendum: Lab results as follows:

-Urine amino acids, urine organic acids, and quantitative serum amino acids-normal
-High resolution chromosomes and FISH for 22q11-normal
-Copper and ceruloplasmin-normal

December 5,2002

HISTORY AND PHYSICAL EXAMINATION

RE: ASCHDON BIRKLE

DOB: 05-07-99

HISTORY OF PRESENT ILLNESS: This patient is a 3-1/2 year old who suffers from spinal muscular atrophy type II. This disorder largely has been a progressive disorder which has slowly taken away Aschdon’s ability in terms of muscle function. This disorder also places him at a higher risk for both muscle contractures as well as for respiratory illnesses and ultimately pneumonia die to decreased respiratory drive and inability to clear his own secretions. October 4, 2002, Aschdon underwent a surgery both to do a Nissen’s fundoplication as well as for a G-Tube placement. Since being discharged from the Salt Lake City Hospital after the G-tube has been placed, he has been on a pump feeds largely at night and also during the day due to his poor oral intake. These feeds have actually improved his overall health. He has been less prone to upper respiratory infections. His strength has been some what improved as well as his overall energy level.

PAST MEDICAL HISTORY: (1) Spinal muscular atrophy type II. (2) RSV bronchiolitis. (3) Pneumonia, multiple hospital admissions. (4) Frequent otitis media. (5) Frequent pharyngitis and tonsillitis.

PAST SURGICAL HISTORY: (1) Status post tympanostomy tubes bilaterally in August 2001. (2) Status post tonsillectomy in May of 2002. (3) Status post Nissen’s fundoplication and G-tube placement October 4, 2002.

MEICATIONS: (1) Albuterol nebulizers on a prn basis. (2) Mucomyst nebulizers on a prn basis. (3) Vivonex feeds; he receives 32 ounces each night.

ALLERGIES: No known allergies.

SOCIAL HISTORY: Lives with his parents and his two other siblings in Wheatland, Wyoming

PHYSICAL EXAMINATION: Temperature 98.4. Pulse 96. Respirations 24. GENERAL: A 3-1/2 year old male who is very thin and has obvious sequelae of spinal muscular atrophy. Head atraumatic, normocephalic. Extraocular muscles intact. Pupils are equal, round and react to light and accommodation. Does have the presence of some allergic shiners bilaterally. His tympanica membranes are clear. Posterior pharynx: Tonsils are absent. There is no posterior erythema or exudates. Neck no lumphadenopathy. Chest no grunting, flaring or retracting, otherwise clear. Abdomen is soft. He does have the presence of a G-tube button in place. There is no surrounding erythema or drainage at this time. No hepatosplenomegaly. Extremities: Very thin in appearance. Very poor muscular tone and coordination. No clubbing, cyanosis or edema noted. Skin: He does have some light yellowing of his face as well as of his hands.

ASSESSMENT:

(1) 3-1/2 year old with spinal muscular atrophy type II.

(2) Nightly tube feeds through his G-tube.

PLAN: This child would benefit from new equipment in terms of a smaller more portable flexible feeding pump. This would assist in the Mother being able to utilize his feeding more adequately during the day as well as at night. A prescription has been written for that. We await response from Home Therapy.

JEREMY M. KATZMANN, M.D., F.A.B.F.P.