Mar 30, 2026

The participant is a 34-year-old woman who developed episodic muscle weakness and pain beginning at age 9. Episodes are characterized by acute worsening of weakness, including paralysis, and last from hours to days. Triggers include physical exertion, fasting, illness, stress, and temperature extremes.

Symptoms progressed significantly in early adulthood, leading to severe fatigue, reduced mobility, and loss of function. At peak severity, the participant was unable to sit upright for extended periods, slept most of the day, and required use of a power wheelchair.

The participant’s clinical course demonstrates a pattern consistent with a disorder of energy metabolism. Symptoms worsen with fasting and delayed meals and improve with carbohydrate intake. She experienced meaningful improvement with overnight cornstarch and Glycosade, consistent with benefit from sustained carbohydrate supplementation. Symptoms are also triggered by high-fat intake and alcohol.

In 2023, the participant initiated treatment with high-dose riboflavin (vitamin B2) and coenzyme Q10, resulting in rapid and significant improvement in strength, endurance, and function, including the ability to walk and return to work.

Genetic and metabolic evaluation has identified variants in the ETFDH and ENO3 genes but has not yielded a definitive diagnosis. The overall phenotype (episodic weakness, fasting intolerance, fat intolerance, response to carbohydrate supplementation, and riboflavin responsiveness) is suggestive of an atypical or incompletely characterized disorder of energy metabolism, including a GA2/MADD-like presentation.

The participant experiences recurrent episodes of acute worsening triggered by physical exertion, fasting or delayed meals, high-fat intake, eating MCT oils (including coconut and palm), alcohol, illness, stress, and temperature extremes. Symptoms during these episodes include:

• Muscle weakness
• Paralysis
• Severe fatigue
• Muscle pain
• Sensation of feeling cold with shivering
• Bradycardia
• Low oxygen saturation
• Dark urine

Outside of these episodes, ongoing symptoms include:

• Muscle weakness
• Chronic fatigue
• Exercise intolerance
• Muscle pain
• Difficulty walking
• Gait disturbance (scissor gait and ataxia)
• Decreased endurance
• Reduced aerobic capacity
• Joint hypermobility

The participant has been diagnosed with the following conditions:

• Postural orthostatic tachycardia syndrome (POTS)
• Mast cell activation syndrome (MCAS)
• Asthma
• Obstructive sleep apnea
• REM sleep behavior disorder
• Restless leg syndrome
• Spinal deformities (lumbar hyperlordosis, scoliosis, L5–S1 spondylolisthesis, and spondylarthritis)
• Endometrial intraepithelial neoplasia (EIN), status post hysterectomy
• Cleft lip and palate, status post repair

• High-dose riboflavin (vitamin B2) has led to significant improvement in muscle strength, endurance, and fatigue
• Coenzyme Q10
• Dietary changes: high-carbohydrate diet with frequent intake and avoidance of high-fat foods, MCT oil, coconut oil, palm oil, alcohol, and fasting
• Xopenex (levalbuterol) – asthma
• Duloxetine – chronic pain and POTS
• Cromolyn sodium – MCAS
• Cetirizine (Zyrtec) – MCAS
• Melatonin – REM sleep behavior disorder
• Iron supplementation – anemia

• Levocarnitine (worsened symptoms)
• Glycosade (extended-release carbohydrate therapy)
• Uncooked cornstarch (overnight carbohydrate supplementation)
• Ketogenic diet (initial symptomatic improvement, but unable to achieve sustained ketosis)

• Sodium D,L-3-hydroxybutyrate (NaHB)