All forms of MDDS are very rare. MDDS causes a wide range of symptoms, which can appear in newborns, infants, children, or adults, depending on the class of MDDS; within each class symptoms are also diverse.

In MDDS associated with mutations in "TK2", infants generally develop normally, but by around two years of age, symptoms of general muscle weakness (called "hypotonia"), tiredness, lack of stamina, and difficulty feeding begin to appear. Some toddlers start to lose control of the muscles in their face, mouth, and throat, and may have difficulty swallowing. Motor skills that had been learned may be lost, but generally the functioning of the brain and ability to think are not affected.

In MDDS associated with mutations in "SUCLA2" or "SUCLG1" that primarily affect the brain and muscle, hypotonia generally arises in infants before they are 6 months old, their muscles begin wasting away, and there is delay in psychomotor learning (learning basic skills like walking, talking, and intentional, coordinated movement). The spine often begins to curve (scoliosis or kyphosis), and the child often has abnormal movements (dystonia, athetosis or chorea), difficulty feeding, acid reflux, hearing loss, stunted growth, and difficulty breathing that can lead to frequent lung infections. Sometime epilepsy develops.

In MDDS associated with mutations in "RRM2B" that primarily affect the brain and muscle, there is again hypotonia in the first months, symptoms of lactic acidosis like nausea, vomiting, and rapid deep breathing, failure to thrive including the head remaining small, delay or regression in moving, and hearing loss. Many body systems are affected.

In MDDS associated with mutations in "DGUOK" that primarily affect the brain and the liver, there are two forms. There is an early-onset form in which symptoms arise from problems in many organs in the first week of life, especially symptoms of lactic acidosis as well as low blood sugar. Within weeks of birth they can develop liver failure and the associated jaundice and abdominal swelling, and many neurological problems including developmental delays and regression, and uncontrolled eye movement. Rarely within class of already rare diseases, symptoms only relating to liver disease emerge later in infancy or in childhood.

In MDDS associated with mutations in "MPV17" that primarily affect the brain and the liver, the symptoms are similar to those caused by DGUOK and also emerge shortly after birth, generally with fewer and less severe neurological problems. There is a subset of people of Navajo descent who develop Navajo neurohepatopathy, who in addition to these symptoms also have easily broken bones that do not cause pain, deformed hands or feet, and problems with their corneas.

In MDDS associated with mutations in "POLG" that primarily affect the brain and the liver, the symptoms are very diverse and can emerge anytime from shortly after birth to old age. The first signs of the disease, which include intractable seizures and failure to meet meaningful developmental milestones, usually occur in infancy, after the first year of life, but sometimes as late as the fifth year. Primary symptoms of the disease are developmental delay, progressive intellectual disability, hypotonia (low muscle tone), spasticity (stiffness of the limbs) possibly leading to quadriplegia, and progressive dementia. Seizures may include epilepsia partialis continua, a type of seizure that consists of repeated myoclonic (muscle) jerks. Optic atrophy may also occur, often leading to blindness. Hearing loss may also occur. Additionally, although physical signs of chronic liver dysfunction may not be present, many people suffer liver impairment leading to liver failure.

In MDDS associated with mutations in "PEO1"/"C10orf2" that primarily affect the brain and the liver, symptoms emerge shortly after birth or in early infancy, with hypotonia, symptoms of lactic acidosis, enlarged liver, feeding problems, lack of growth, and delay of psychomotor skills. Neurologically, development is slowed or stopped, and epilepsy emerges, as do sensory problems like loss of eye control and deafness, and neuromuscular problems like a lack of reflexes, muscular atrophy, and twitching, and epilepsy.

In MDDS associated with mutations in the genes associated with mutations in "ECGF1"/"TYMP" that primarily affects the brain and the gastrointestinal tract, symptoms can emerge any time in the first fifty years of life; most often they emerge before the person turns 20. Weight loss is common as is a lack of the ability of the stomach and intestines to automatically expand and contract and thus move through it (called gastrointestinal motility) – this leads to feeling full after eating only small amounts of food, nausea, acid reflux, All affected individuals develop weight loss and progressive gastrointestinal dysmotility manifesting as early satiety, nausea, diarrhea, vomiting, and stomach pain and swelling. People also develop neuropathy, with weakness and tingling. There are often eye problems, and intellectual disability.

MDDS are a group of genetic disorders that share a common pathology — a lack of functioning DNA in mitochondria. There are generally four classes of MDDS:

- a form that primarily affects muscle associated with mutations in the "TK2" gene;

- a form that primarily affects the brain and muscle associated with mutations in the genes "SUCLA2", "SUCLG1", or "RRM2B";

- a form that primarily affects the brain and the liver associated with mutations in "DGUOK", "MPV17", "POLG", or "PEO1" (also called "C10orf2"); and

- a form that primarily affects the brain and the gastrointestinal tract associated with mutations in "ECGF1" (also called "TYMP").

Mal de debarquement (or mal de débarquement) syndrome (MdDS, or common name disembarkment syndrome) is a neurological condition usually occurring after a cruise, aircraft flight, or other sustained motion event. The phrase "mal de débarquement" is French for "sickness from disembarkation".

MdDS is typically diagnosed by a neurologist or an ear nose & throat specialist when a person reports a persistent rocking, swaying, or bobbing feeling (though they are not necessarily rocking). This usually follows a cruise or other motion experience. Because most vestibular testing proves to be negative, doctors may be baffled as they attempt to diagnose the syndrome. A major diagnostic indicator is that most patients feel better while driving or riding in a car, i.e.: while in passive motion. MdDS is unexplained by structural brain or inner ear pathology and most often corresponds with a motion trigger, although it can occur spontaneously. This differs from the very common condition of "land sickness" that most people feel for a short time after a motion event such as a boat cruise, aircraft ride, or even a treadmill routine which may only last minutes to a few hours. The syndrome has recently received increased attention due to the number of people presenting with the condition and more scientific research has commenced to determine what triggers MdDS and how to cure it.

Symptoms most frequently reported include a persistent sensation of motion usually described as rocking, swaying, or bobbing, disequilibrium with difficulty maintaining balance; it is seldom accompanied by a true spinning vertigo. Chronically fatigued, sufferers can become fatigued quickly with minimal exertion and experience neck and back pain. Other common symptoms include difficulty concentrating or inability to multitask, visual intolerance of busy patterns, headaches and/or migraine headaches, and ear pain or fullness.

Fluctuations in weather, in particular barometric pressure, also affect suffers. Many have photo-sensitivity and find it more difficult to walk in the dark as well as other sensitivities to strong smells including chemical smells. Cognitive impairment ("brain fog") includes an inability to recall words, short term memory loss, an inability to multi-task, misspelling and mispronunciation of words. MdDS sufferers report they are unable to use a computer for any length of time due to the visual overstimulation, and some are even unable to watch television.

The condition may be masked by a return to motion such as in a car, train, plane, or boat; however, once the motion ceases, the symptoms rebound or return, often at much higher levels than when the journey first commenced. Symptoms can be increased by stress, lack of sleep, crowds, flickering lights, loud sounds, fast or sudden movements, enclosed areas or busy patterns.

MdDS sufferers can sleep up to 12 or more hours a day, depending on their symptom levels. Research reveals MdDS is not migraine related and many sufferers have never had migraine symptoms prior to the onset of the disorder. However, for some MdDS sufferers there maybe have been a correlation between migraine and some pathophysiological overlap or even some other precipitating illness.

The symptoms of MdDS may be extremely debilitating and fluctuate high and low on a daily basis; it greatly affects the working capacity of sufferers with many having to relinquish work; it also limits most other daily and social activities. Sufferers can have low quality of life in both the physical and emotional realms, comparable to people who have multiple sclerosis.