- Elevated circulating creatine kinase activity (HP:0003236): The activity of creatine kinase in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/6. (PMID:23313956)
- Facial palsy (HP:0010628): Facial nerve palsy is a dysfunction of cranial nerve VII (the facial nerve) that results in inability to control facial muscles on the affected side with weakness of the muscles of facial expression and eye closure. This can either be present in unilateral or bilateral form. Evidence: TAS. (OMIM:615084)
- Progressive (HP:0003676): Applies to a disease manifestation that increases in scope or severity over the course of time, i.e., that worsens with age. Evidence: PCS. (PMID:23313956)
- Cerebellar atrophy (HP:0001272): Cerebellar atrophy is defined as a cerebellum with initially normal structures, in a posterior fossa with normal size, which displays enlarged fissures (interfolial spaces) in comparison to the foliae secondary to loss of tissue. Cerebellar atrophy implies irreversible loss of tissue and result from an ongoing progressive disease until a final stage is reached or a single injury, e.g. an intoxication or infectious event. Evidence: PCS. Frequency: 5/5. (PMID:23313956)
- Arrhythmia (HP:0011675): Any cardiac rhythm other than the normal sinus rhythm. Such a rhythm may be either of sinus or ectopic origin and either regular or irregular. An arrhythmia may be due to a disturbance in impulse formation or conduction or both. Evidence: PCS. Frequency: 1/6. (PMID:23313956)
- Hypergonadotropic hypogonadism (HP:0000815): Reduced function of the gonads (testes in males or ovaries in females) associated with excess pituitary gonadotropin secretion and resulting in delayed sexual development and growth delay. Evidence: TAS. (OMIM:615084)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: TAS. (OMIM:615084)
- Young adult onset (HP:0011462): Onset of disease at the age of between 16 and 40 years. Evidence: PCS. (PMID:23313956)
- Proximal amyotrophy (HP:0007126): Amyotrophy (muscular atrophy) affecting the proximal musculature. Evidence: TAS. (OMIM:615084)
- Nausea (HP:0002018): A sensation of unease in the stomach together with an urge to vomit. Evidence: TAS. Frequency: Occasional (HP:0040283). (OMIM:615084)
- Spinal rigidity (HP:0003306): Reduced ability to move the vertebral column with a resulting limitation of neck and trunk flexion. Evidence: PCS. Frequency: 2/6. (PMID:23313956)
- Intellectual disability (HP:0001249): The term intellectual disability or intellectual developmental disorder is used to describe significantly sub-average intellectual and adaptive functioning based on clinical assessment and as measured by individually administered, appropriately normed, standardized and validated tests of intellectual functioning and adaptive behavior, with onset during the developmental period from infancy through adolescence. Evidence: PCS. Frequency: 3/6. (PMID:23313956)
- Dilated cardiomyopathy (HP:0001644): Dilated cardiomyopathy (DCM) is defined by the presence of left ventricular dilatation and left ventricular systolic dysfunction in the absence of abnormal loading conditions (hypertension, valve disease) or coronary artery disease sufficient to cause global systolic impairment. Right ventricular dilation and dysfunction may be present but are not necessary for the diagnosis. Evidence: PCS. Frequency: 1/6. (PMID:23313956)
- Exercise intolerance (HP:0003546): A functional motor deficit where individuals whose responses to the challenges of exercise fail to achieve levels considered normal for their age and gender. Evidence: PCS. (PMID:23313956)
- Generalized amyotrophy (HP:0003700): Generalized (diffuse, unlocalized) amyotrophy (muscle atrophy) affecting multiple muscles. Evidence: PCS. Frequency: 5/6. (PMID:23313956)
- Multiple mitochondrial DNA deletions (HP:0003689): The presence of multiple deletions of mitochondrial DNA (mtDNA). Evidence: PCS. Frequency: 6/6. (PMID:23313956)
- Hyporeflexia (HP:0001265): Reduction of neurologic reflexes such as the knee-jerk reaction. Evidence: PCS. Frequency: 2/6. (PMID:23313956)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/6. (PMID:23313956)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. (PMID:23313956)
- Ragged-red muscle fibers (HP:0003200): An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm. Evidence: PCS. Frequency: 6/6. (PMID:23313956)
- Easy fatigability (HP:0003388): Increased susceptibility to fatigue. Evidence: TAS. (OMIM:615084)
- Progressive external ophthalmoplegia (HP:0000590): Initial bilateral ptosis followed by limitation of eye movements in all directions and slowing of saccades. Evidence: PCS. Frequency: 6/6. (PMID:23313956)
- Dyspnea (HP:0002094): Difficult or labored breathing. Dyspnea is a subjective feeling only the patient can rate, e.g., on a Borg scale. Evidence: PCS. (PMID:23313956)
- Respiratory insufficiency (HP:0002093). Evidence: PCS. Frequency: 2/6. (PMID:23313956)
- Decreased activity of mitochondrial complex I (HP:0011923): A reduction in the activity of the mitochondrial respiratory chain complex I, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 4/4. (PMID:23313956)
- Dysphonia (HP:0001618): Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause. Evidence: PCS. Frequency: 2/6. (PMID:23313956)
- Kyphosis (HP:0002808): Exaggerated anterior convexity of the thoracic vertebral column. Evidence: PCS. Frequency: 4/6. (PMID:23313956)
- Ptosis (HP:0000508): The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective). Evidence: PCS. (PMID:23313956)
- Autosomal recessive inheritance (HP:0000007): A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in individuals with two pathogenic alleles, either homozygotes (two copies of the same mutant allele) or compound heterozygotes (whereby each copy of a gene has a distinct mutant allele). Evidence: PCS. (PMID:23313956)
- Neuropathic spinal arthropathy (HP:0008443): A progressive disorder of vertebral joint degeneration that occurs in the setting of any condition characterized by decreased afferent innervation, involving loss of deep pain and proprioceptive sensation in the vertebral column. Patients most commonly present with symptoms of lower back pain, sitting imbalance, progressive spinal deformity (usually kyphosis), and an audible clicking sound on changing postures. Evidence: PCS. (PMID:23313956)
- Decreased activity of mitochondrial complex IV (HP:0008347): A reduction in the activity of the mitochondrial respiratory chain complex IV, which is part of the electron transport chain in mitochondria. Evidence: PCS. Frequency: 2/4. (PMID:23313956)
- Hypernasal speech (HP:0001611): A type of speech characterized by the presence of an abnormally increased nasal airflow during speech associated with structural abnormality of the nasal passages. Evidence: PCS. (PMID:23313956)
- Chronic diarrhea (HP:0002028): The presence of chronic diarrhea, which is usually taken to mean diarrhea that has persisted for over 4 weeks. Evidence: PCS. Frequency: 2/6. (PMID:23313956)
These phenotypes are associated with the disease mitochondrial DNA depletion syndrome 11 (OMIM:615084).