The Inherited Metabolic Disorders News

Hello everyone! I hope you have had an opportunity this summer to enjoy a little rest and relaxation with family and friends. We are happy to share our recent clinic updates with you and look forward to hearing your feedback.

Suzanne Nurse

Dear Friends,

Greetings! Hope you all are enjoying the summer weather. The theme of this newsletter is how to find opportunities in times of uncertainty. The metabolic patients, families and the metabolic team are no strangers to uncertainty. We are sharing the story of the Blake family, their courage during difficult times. I am pleased to see that Lyla (their daughter) is now a teenager and doing very well with support from the family, Dr. Kambiz Norozi (cardiologist) and the metabolic team. As they say it takes a village to raise a child (African Proverb). Grandparents, sib-lings, family and friends play a very essential role as caregivers and are the best cheerleaders for the patients and their families.

Meghan Zadorsky, many of you might remember was instrumental in bring-ing out the metabolic newsletters some time back. I’m very happy that Me-ghan has now returned to our genetics team as a genetic counsellor and will be providing genetic counselling support to Dr. Natalya Karp’s patients. Wel-come Meghan! Dr. Montaha Almudhry completed her one-year neurometa-bolic fellowship successfully with Dr. Narayan Prasad, Dr. Tony Rupar and myself. She has met many of our patient families and has been involved in a number of research projects. We wish her the best in her academic future.

Averi Nooren has joined as metabolic social worker (covering Carrie Char-ters’ leave). Thanks Averi. I would like to thank the CHEO Newborn Screen-ing program for providing support for the addition of two new metabolic team members. Welcome Vanessa Mahon (metabolic nurse) Vanessa So (registered dietitian)!

It has been wonderful seeing many of you in person and hope this continues. A big thanks to the metabolic team for their dedication and commitment.

I am grateful to Suzanne Nurse for being the editor of this metabolic newslet-ter and the previous one.

We are planning our next metabolic family workshop on the 26th April 2024. Hope to see you all there. Please save the date.

Stay safe!
With very best wishes
Chitra Prasad

Lyla Blake

Jeff and I are parents to a thriving 14-year-old girl who amazes us, surprises and yes at times even challenges us – she is a teenager after all. Lyla was born in the spring of 2009 and was the love of our lives instantly. Although Jeff and I are no longer a couple we can eas-ily say that we are still a family it just looks different. The challenges our family have overcome in those early years have created a special bond for our family. Our family's journey with our child's undiagnosed genetic disorder was an extremely challenging and emotional experi-ence. For a year, we watched our child struggle with various health issues, and we were left feeling helpless and frustrated as doctors were unable to provide us with a diagnosis. It was a time of uncertain-ty and worry, which left us desperate for answers.

Finally, after a year of searching, we received a diagnosis. Our child had a rare genetic disorder which was misdiagnosed and impacted her heart, and we were told that there was no cure. We were devas-tated by the news, and we felt overwhelmed by the prospect of man-aging our child's condition for the rest of their life. We were in discus-sion about heart transplants and how she was going to regain her energy and heart function to live a normal life. Conversations that no parent ever thinks they are going to have. To say that our life seemed to be crashing around us would be an understatement.

Learning about our child's diagnosis was a difficult experience, but it also brought our family closer together. We rallied around Lyla, and we worked together to provide her with the care and support she needed. We learned everything we could about our child's condition, and we worked closely with doctors and specialists to develop a treatment plan.

Despite the challenges, our family found strength in our shared experience. We learned to appreciate the small moments of joy and happiness in our lives, and we became more resilient in the face of adversity. We also became advocates for not only Lyla but also for improving the system. Looking back on our journey, we realize that our family's experience has taught us many valuable lessons. We have learned the importance of perseverance, resilience, and the power of love and support. We have also learned to appreciate the fragility of life and to cherish every moment we have with our loved ones.

Parents of children with undiagnosed heart conditions, or other serious medical condi-tions, may also feel isolated and alone. They may feel like no one else understands what they are going through, and may struggle to find support from friends and family mem-bers who don't fully grasp the severity of their child's condition. This can lead to feel-ings of loneliness and despair, which can further exacerbate their fears and anxieties.

We look back on this time and think it seems like another life. Lyla is graduating grade 8 this year and I can’t believe she is entering high school. Due to the support from the amazing healthcare team, Lyla has been able to participate in gymnastics, dance, and horseback riding. She is very active and is now training to compete in boxing. Lyla loves her many animals. Between Jeff and my house, she has 2 dogs and 4 cats plus at Grandma’s she has 3 cats and a dog. She spends lots of time with Grandma and they talk every day. Lyla has a passion for travel and has been fortunate enough to be on many cruises and just recently returned from Punta Cana with mom and Grandma.

This was a very difficult journey but with unbelievable dedication and support from Lyla’s doctors and nurses we were able to eventually have the confidence and trust that our child was going to return to normal activity. You cannot imagine the feeling of thinking that the other shoe was going to drop and your child would be back in hospital and possibly in a worse situation. The doctors and nurses are the true heroes. Despite a rough beginning to life, Lyla has flour-ished and is a strong, smart young lady.

Carnitine Uptake Disorder or Primary Carnitine Deficiency

Primary carnitine deficiency is a genetic con-dition that prevents the body from using cer-tain fats for energy, particularly during peri-ods without food (fasting). The nature and severity of signs and symptoms may vary, but they most often appear during infancy or ear-ly childhood and can include severe brain dysfunction (encephalopathy), cardiomyopathy, confu-sion, vomiting, muscle weakness, and hypoglycemia (low blood sugar). Some individuals may only have fatigability in adult-hood, or no symptoms at all. This condition is caused by mutations in the SLC22A5 gene and is inherited in an autosomal reces-sive manner. Treatment and prevention of symptoms typically includes high doses of oral L-carnitine supplementation. Regular cardiac follow up and management of cardio-myopathy is important. This disorder is in-cluded now in the newborn screening.

The primary function of the plasma mem-brane carnitine transporter. Mutations of its encoding gene SLC22A5 (previously called OCTN2) result in impairment of carnitine up-take and significant reduction of intracellular carnitine level. This plasma membrane car-nitine transporter is crucial for uptake of car-nitine into heart and skeletal muscle which are dependent on fatty acid oxidation for energy supply. It is also required in reabsorption of carnitine from tubular fluid back to the circulation in renal tubules.

Dr. Kambiz Norozi, Paediatric Cardiologist

Originally from Persia, I trained as a Pediatrician and specialized as a Paediatric Cardiologist in Ger-many, earning my PhD from Hannover Medical School in 2007. After relocating to Canada in 2008, I collaborated with scientists at Children’s Health Research Institute, focusing on cardiovascular imag-ing and heart development in animal models. Concurrently, I expanded my research to assess risk factors for cardiovascular disorders in obese children.

While my rewarding research continues, my clinical commitment lies in ensuring a smooth transition for Paediatric Cardiology patients to adult care. Currently, I actively contribute to establishing a specialized transition clinic for adolescents and young adults with congenital heart defects. My unwavering dedication drives me to provide exceptional care and support during this critical phase of their medical journey.

Tips and Tricks When Cooking with Low Protein Products by Vanessa So

On June 16th I attended a cooking seminar held by one of the low protein food manufacturers, Cambrooke. I was able to work and experiment with some of the low protein products that many patients use regularly. One of the main motiva-tions for attending the cooking seminar was from hearing feedback from patients about how difficult some of the prod-ucts are to work with.
Here are a few tips and tricks that I gathered when working with a few of the low-protein Cambrooke foods -- specifical-ly, the “Eggz” and “MixQuick” baking mix.

1) Sometimes, less is more! One of the major frustrations with these products is figuring out how to cook the product and how to troubleshoot the issues. With both products starting as a powder, liquid is necessary to make the product work. However, one of the most common mistakes is actually adding too much liquid to the recipe, resulting in a gummy product that doesn’t quite cook evenly. Since most of these products are starch based to reduce the protein content, the extra water reacts with the starches in a way that produces a gel instead of a solid, cooked product which won’t cook correctly, no matter how long you cook it. When using the Mix Quick to make pancakes, it may seem second nature to add enough liquid to make it your typical “pancake consistency”. However, we quickly learned that the few extra tablespoons of water were detrimental to the fi-nal product. The best final product had the most “questionable” batter consistency (lumpy, paste-like) but resulted in a fluffy and thoroughly cooked pancake. The amount of water outlined on the product instructions ended up being the cor-rect amount needed for a desirable finished product. It was also noted that elevation can have an impact on the amount of water used. Below are some examples of the varying consistencies, depending on the amount of water added.

2) Waffle makers are amazing!
The waffle maker was a great cooking appliance to use for both the MixQuick
and the Eggz. Since there are 2 sides of heated elements, the batter cooks quickly and more evenly. The extra grooves in a waffle iron add extra crunch to what you’re making which provides contrast to the soft and bouncy texture of most low protein foods. Small sized waffle makers are relatively inexpensive and very easy to cook with.

3) Use oils/fats when cooking for more appealing colour
Part of the reason why foods get a “golden brown colour” when cooked is due to a combination of sugars
and protein in a process called the “Maillard reaction”. Since the protein content of low protein foods is signif- icantly lower, there can be a noticeable difference in appearance of low protein foods. They often look paler and almost undercooked because of this. The extra direct surface area from a waffle maker can help with this issue but when using a flat surface such as a pan, even if it’s non-stick, ensuring that there is a light layer of
fat or oil will help create some browning on foods to make the appearance more appetizing.
We’ve come a long way from bread in a can! For those of you who may have been around to remember.

Margie’s Summer Vegetable Spaghetti

• 2 cups small yellow onion, cut in eighths (335 grams)
• 2 cups tomatoes, chopped, peeled, fresh and ripe (450 grams)
• 1 1/2 cups yellow and green squash (340 grams)
• 1 1/2 cups fresh green beans (225 grams)
• 2/3 cup water
• 2 Tablespoons fresh parsley, minced
• 1 clove garlic, minced
• 1/2 teaspoon chili powder
• 1/4 teaspoon salt
• 1/8 teaspoon freshly ground black pepper
• 1/2 can tomato paste (3 oz)
• 1 pound uncooked low protein spaghetti*

Combine the first 10 ingredients in large saucepan; cook for 10 minutes, then stir in tomato paste. Cover and cook gently, 15 minutes, stirring occasionally until vegetables are tender. Cook spaghetti in unsalted water according to package directions. Spoon sauce over drained hot spaghetti.

Makes 9 servings

Per serving (½ cup spaghetti and ¼ cup sauce) = 89mg phe or 2.9g protein

*This recipe was re-calculated using Aproten spaghetti as Loprofin spaghetti is no longer available. Recipe adapted from aboutproduce.com, June 2002

Neonatal hyperinsulinism-broadening the differential diagnosis. Emma Metivier , Madhavi Prasad , Chitra Prasad. Paediatr Child Health, 2022 Dec 16;28(2):67-68.
Severe developmental delay and behaviour abnormalities in a patient with de novo CAMK2B mutation: A case report and literature review. K. Zhang, C.A Rupar C. Prasad. Child Health Research Day poster presentation.
Investigation of a TRIM28 gene variant identified in a paediatric patient presenting with in-tellectual disability Authors: Namavari, Niloofar, Prasad, C. and Bérubé, NG. Child Health Research Day poster presentation.
When Fasting Turns Fatal: Eating Disorders in Patients with Medium-Chain Acyl-CoA Dehydrogenase Deficiency. Mia B. Sethna, Natalya Karp, Tony Rupar, Suzanne Ratko, Chitra Prasad (Presented at Garrod meeting 2023 oral presentation) and also at Child Health Research Day.
A Milder form of Molybdenum cofactor deficiency type A presenting as Leigh's syndrome-like phenotype and highlighting the secondary mito-chondrial dysfunction in this entity. Montaha Almudhry, Asuri N. Prasad, C. Anthony Rupar, Keng Yow Tay, Suzanne Ratko, Mary Jenkins, Chitra Prasad. (Poster at Garrod meeting).
14-month-old boy with severe VLCAD deficiency on Triheptanoin (Dojolvi) in the past 6 months: our experience. S Pathak, M Sethna, C Prasad, L Altamirano-Diaz, M McClean, S Ratko, V So, T Rupar and N Karp. (Garrod meeting poster presentation)

Dr. Mia Sethna, Garrod meeting 2023
Methylmalonic aciduria: a clue to diagnosis of hypotonia, developmental delay and movement disorders associated with SUCLA2 and SULG1 gene mutations. “A case series” Montaha Almudhry, Mohammed Alomri, Asuri N. Prasad, Maryam Nouri, Arushi Gahlot Saini, Andrea Yu, C. Ant-hony Rupar, and C. Prasad (Poster at Garrod meeting). Presenter (left-hand side): Dr. Montaha Almudhry
Good short-term outcome and resolution of hepatic fail-ure, coagulopathy, hypoglycemia and lactic acidosis in a 5-month-old with TRMU-related disorder.
Authors: Jessica Garabon, Chitra Prasad, Dhandapani Ashok, Farah Abdulsatar, Tony Rupar, Suzanne Ratko, Samantha, Colaiacovo, Natalya Karp (Poster at Garrod meeting).
Presenter (right-hand side): Dr. Jessica Garabon
Parent and healthcare personnel perspectives on challenges to family-centred care for children with inherited met-abolic diseases: a qualitative analysis of interview data. Andrea Chow, Isabel Jordan, Nicole Pallone, Maureen Smith, Pranesh Chakraborty, Zobaida Al-Baldawi, Jamie Brehaut, Alicia KJ Chan, Eyal Cohen, Sarah Dyack, Lisa Jane Gillis, Sharan Goobie, Ian D. Graham, Cheryl R. Greenberg, Jeremy M. Grimshaw, Robin Hayeems, Michal Inbar-Feigenberg, Shailly Jain-Ghai, Sara Khangura, Jennifer J. MacKenzie, Nathalie Major, John J. Mitchell, Stu-art G. Nicholls, Amy Pender, Murray Pottey, Chitra Prasad, Natalya Karp, Andreas Schulze, Komudi Siriwardena, Rebecca Sparkes, Kathy N. Speechley, Sylvia Stockler, Yannis Trakadis, Clara van Karnebeek, Jagdeep S. Walia, Brenda J. Wilson, Kumanan Wilson, Andrea C. Yu, and Beth K. Potter. (Garrod meeting presentation).

Long term follow-up of an attenuated case of PEBEL1 due to NAXE gene mutation: Expanding the phenotypic variability of a potentially modifiable disease. Montaha Almudhry, Chitra Prasad, C. Anthony Rupar, Keng Yow Tay and Asuri N. Prasad (Poster at Garrod meeting).