A Challenging Case of an "Unknown" Mitochondrial Disorder in a 17-Year-Old Male
The combination of organic acids testing and buccal swab analysis of electron transport chain activity
This patient case comes from my consulting practice working with complex neurodevelopmental and chronic health disorders. This individual was not considered a special needs individual, i.e., a person with autism, but instead is a neurotypical young man with a rapid onset health deterioration following an “unknown” illness that occurred in adolescence.
This case highlights the usefulness of two integrative medicine lab tests. One is the Organic Acids Test (OAT) from Mosaic Diagnostics Laboratory and the other is a buccal swab profile from MITOswab.
The patients main issues include the following:
Inborn-error defect within the electron transport chain (ETC) - “cells not making enough ATP with most of the problem in skeletal muscles.”
Progressive weakness, poor exercise tolerance. Cannot run or ride bike.
Easily fatigued
Clinical History:
At the age of 8 he started having issues with physical activity such as surfing and water polo. Complained of being weak and tired.
Developed a bad “flu-like illness” and within 3 weeks had major deterioration with vomiting episodes and progressive weakness.
Whenever he gets sick or over-stressed his condition can worsen
This individual has had extensive laboratory testing for various metabolic disorders, genetics, environmental exposures, including mold and mycotoxins. From a conventional medical standpoint there is evidence of a ETC dysfunction, although genetically the exact location has not been established.
The first test result is a MITOswab Profile (image 1) which evaluates from a buccal swab the activity within the mitochondria of various ETC proteins. The MITOswab has been shown in previous studies to have approximately a 84% correlation with Complex I (C-I) and Complex IV (C-IV) with the ETC compared to the gold standard muscle biopsy analysis.
Image 1 - these test results show a normal activity of citrate synthase (CS) which is the rate-limiting first step in Krebs cycle activity. His C-IV is elevated which is a likely a compensatory reaction to low C-I and C-II/III (see below). However, C-I activity is below the normal range.
C-I deficiency is the most common point in the ETC to be defective. C-I is the largest protein complex in the ETC and is the greatest point of electron leakage into the mitochondrial matrix. Poor C-I leads to excess oxygen radical formation within the mitochondria. Another point of electron leakage occurs from problems in C-III (image 2).
Image 2 - the MITOswab profile detected normal activity of C-II, but deficient activity the supercomplex II-III. Complex III is the final point of transfer of electrons to complex IV.
What this test information reveals is major points within the ETC that compromise electron transfer and ultimately poor production of adenosine triphosphate (ATP). The increased activity of C-IV may be a compensatory mechanism to offset poor activity of C-I and C-II/III.
Mitochondrial problems often lead to increase lactic acid (LA). An abundance of LA can lead to lactic acidosis, a form of metabolic acidosis. Prolonged metabolic acidosis (e.g., lactic acidosis) can be stressful on the body, and lead to depletion of acid buffers that leaves various organ systems vulnerable to damage, including the brain, nervous system, liver, kidneys, and muscles. Image 3 shows a chart of lactic acid markers over multiple years.
Image 3 - notice that all lactic acid levels from 2018 thru 2022 are elevated, except for 2020. Lactic acid levels can fluctuate depending on various factors happening within a person’s metabolism and mitochondrial activity. Times of lower stress may allow for more “normal” activity for a period of time.
The following image is from a 2020 OAT showing high normal LA which correlates with a normal 2020 blood LA. One additional marker to recognize is 3-hydroxyglutaric which is elevated at 77.
Image 4 - this is a 2020 OAT profile showing high normal lactic acid and high 3-hydroxyglutaric at 77. Typically, values greater than 60 mmol/mol are seen in glutaric aciduria.
The following OAT is from 2022. The LA is elevated at 22 (which correlates with his blood LA test), and his 3-hydroxyglutaric is very high at 126.
Image 5 - the high lactic acid is consistent with the previous blood test he had done for lactic acid. In this test the 3-hydroxyglutaric is even higher at 126.
The high 3-hydroxyglutaric acid is consistent with a form of glutaric acidemia. There are various types of glutaric acidemia and different causes for each. His pattern of OAT markers is consistent with either a type II glutaric acidemia or MADD mild (MADD-M) which is considered a late onset form. The next image is from one of his OATs showing elevated fatty acid metabolites. These can be seen in MADD-M or other forms of glutaric acidemia.
Image 6 - with MADD-M, high ethylmalonic, methylsuccinic, and adipic acids are commonly seen on organic acids testing.
The last OAT from 2024 shows high LA and high 3-hydroxyglutaric acid. The levels are fluctuating, but still significantly elevated.
Image 7 - patient still shows elevated lactic acid, and 3-hydroxyglutaric acid
What makes this case challenging is the overlapping problems of multiple point deficits within the mitochondrial ETC, as well as likely enzyme complex malfunction affecting Lysine amino acid metabolism associated with glutaric acidemia. There is a high potential for oxidative stress within the mitochondria too which greatly compromises other cellular systems leading to overall dysfunction.
A recent blood test analyzing ketone balance of acetoacetic acid and 3-hydroxybutyric acid showed poor redox potential within the mitochondria which adds to the underlying biochemical dysregulation.
A supplement regimen of mitochondrial and antioxidant support was implemented:
ATP 360 - mitochondrial support from Research Nutritionals
L-carnitine, CoQ10, B-vitamins, e.g., thiamine
D-Ribose - helpful for mitochondria ATP production, particularly within the musculoskeletal system
Riboflavin - needed for C-I and C-II
Sulforaphane - aides with antioxidant support
Liposomal Vitamin C - aides in antioxidant protection
Liposomal Glutathione - aides in antioxidant protection
Liposomal Melatonin - assists with ETC activity, antioxidant properties, and down-regulation of aerobic glycolysis which drives elevated lactic acid formation
With regards to his redox deficit affecting acetoacetic acid and 3-hydroxybutyric acid conversion he was also placed on high dose niacin.
The combination of the Organic Acids Test and MITOswab profile is a powerful combination to aide in clinical decision making with regards to mitochondrial dysfunction, as well as other metabolic imbalances that may be occurring in complex disorders.