ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications

[u/alexmadsen1]

[u/alexmadsen1]

Recent research has highlighted a significant overlap between Attention-Deficit/Hyperactivity Disorder (ADHD) symptoms and various neurometabolic diseases (NMDs). This executive summary provides a concise overview of the key findings from the paper, "ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications," and discusses the implications for diagnosis, treatment, and future research.

Key Findings:

1. Prevalence of ADHD Symptoms in Neurometabolic Diseases:
   • ADHD-like symptoms are common in several neurometabolic diseases (NMDs), which are genetic disorders that affect enzyme functions and lead to neurological impairments.
   • Disorders such as phenylketonuria (PKU), tyrosinemias, alkaptonuria, succinic semialdehyde dehydrogenase (SSADH) deficiency, maple syrup urine disease (MSUD), and various mitochondrial disorders frequently exhibit ADHD symptoms. These symptoms include inattention, hyperactivity, and impulsivity, often complicating the clinical presentation of NMDs.
2. Shared Neurochemical Pathways:
   • Many NMDs converge on neurochemical pathways involving monoamine neurotransmitters—dopamine, norepinephrine, and serotonin—which are also central to the pathophysiology of ADHD.
   • The paper describes how disruptions in neurotransmitter synthesis, transport, metabolism, and receptor function, often resulting from specific metabolic defects, contribute to ADHD-like behaviors.
   • For example, PKU is characterized by elevated phenylalanine levels that impair monoamine synthesis, while tyrosinemias disrupt tyrosine metabolism, affecting dopamine and norepinephrine pathways.
3. Impact of Metabolic Disturbances on Neurotransmitter Dynamics:
   • The synthesis and balance of neurotransmitters are crucial for normal brain function. Metabolic disorders that alter the availability or function of critical cofactors (e.g., tetrahydrobiopterin, or BH4) can significantly impact these pathways.
   • The paper highlights how NMDs affect not only monoamine neurotransmitters but also involve broader metabolic pathways, such as the folate cycle and methionine cycle, which are important for maintaining neurological health.
4. Clinical Implications:
   • The recognition of ADHD symptoms in patients with metabolic disorders is essential for accurate diagnosis and effective treatment. Misdiagnosis or delayed diagnosis can lead to inappropriate management and poorer outcomes.
   • A comprehensive treatment approach that addresses both the metabolic disorder and its neuropsychiatric manifestations, including ADHD symptoms, is crucial. This may involve dietary management, medication, and behavioral therapies tailored to the specific metabolic condition..
5. Research Gaps and Future Directions:
   • The paper calls for more research to explore the precise biochemical pathways linking ADHD symptoms and NMDs. Understanding these connections could lead to better-targeted therapies and improved clinical outcomes.
   • Future studies should aim to clarify the role of metabolic dysfunctions in neurodevelopmental disorders, potentially offering new insights into treatment strategies for ADHD and related conditions.

Conclusion:

This review underscores the importance of considering metabolic disorders in the differential diagnosis of ADHD, particularly when symptoms are atypical or resistant to standard treatments. By understanding the shared biochemical and neurochemical mechanisms between ADHD and neurometabolic diseases, clinicians can better tailor their therapeutic approaches, ultimately improving patient care and outcome

Cannon Homaei, S., Barone, H., Kleppe, R., Betari, N., Reif, A., & Haavik, J. (2022). ADHD symptoms in neurometabolic diseases: Underlying mechanisms and clinical implications. Neuroscience and Biobehavioral Reviews, 132, 838–856. https://doi.org/10.1016/j.neubiorev.2021.11.012

[u/sirCota]

i’ve always had adhd(i).
then i had to be hospitalized for pancreatitis.

since then, my pancreas is back to normal, as is my blood work in general, but i’ve had all sorts of weird adrenal fatigue / mitochondrial disfunction style symptoms ranging from nerve pain/tingle mostly on hands and legs. Occasional hypersensitivity to cold, and touch in general … incredible fatigue and body pains, emotional instability. there’s more but it’s not all the time and not all at once. the adhd has gotten much much worse, particularly the brain fog.

at first it seemed tyrosine and DLPA and B vitamins were helpful, then PQQ, CoQ10, fish oil … vit C , creatine, AKG, iron, zinc, magnesium, copper, adrenal supplements , holy basil… and a bunch of other shit… jiaogulan seemed to help for a bit, but eventually i started taking much less of the lesser known supps and much lower dosages in general outside of PQQ, fish oil, and the basic minerals and vitamins… not every day.

The symptoms eventually seemed to become more stable over the course of several months, but they can be triggered at any time.

outside of the tangential supplement list… it really felt like being in the ICU and almost dying triggered a host of weird metabolic stuff, which is a thing i know (and some people link this to long covid, but we don’t need to go down that worm hole). The symptoms weren’t right after the pancreatitis… it took a few months for them to materialize.

in summary, it really feels like my adhd and the symptoms of autoimmune/ adrenal / mitochondrial issues are connected. the worse one is, the worse they all get.

this is all anecdotal, but i sure wish i could read that chart well enough to know if any of the information pertains to me, or what supplements I took that helped or hurt etc. i don’t really care for the supplements anyway.. i didn’t need them for 40 years, im skeptical i need more than a multi-vitamin now. I am awaiting referrals w endocrine and rheumatoid specialists.