- 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: 4/4. (PMID:2850914;PMID:12563048)
- Elevated urine mevalonic acid level (HP:0032638): An abnormally increased amount of mevanolate in the urine. Mevanolate is that hydroxy monocarboxylic acid anion that is the conjugate base of mevalonic acid. Evidence: PCS. Frequency: 7/7. (PMID:2850914;PMID:12563048;PMID:8352861)
- Failure to thrive in infancy (HP:0001531). Evidence: PCS. Frequency: 3/3. Onset: Infantile onset (HP:0003593). (PMID:8352861)
- Short stature (HP:0004322): A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms). Evidence: PCS. Frequency: 3/3. (PMID:12563048)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Hypotonia (HP:0001252): Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist. Evidence: PCS. Frequency: 1/1. Onset: Infantile onset (HP:0003593). (PMID:2850914)
- Ataxia (HP:0001251): Ataxia refers to impaired coordination of voluntary muscle movement. Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly). Evidence: PCS. Frequency: 4/4. (PMID:2850914;PMID:12563048)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. Frequency: 3/3. (PMID:8352861)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: PCS. (PMID:12563048)
- Cataract (HP:0000518): A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule. Evidence: PCS. Frequency: 3/3. (PMID:8352861)
- Nystagmus (HP:0000639): Rhythmic, involuntary oscillations of one or both eyes related to abnormality in fixation, conjugate gaze, or vestibular mechanisms. Evidence: TAS. (OMIM:610377)
- Large fontanelles (HP:0000239): In newborns, the two frontal bones, two parietal bones, and one occipital bone are joined by fibrous sutures, which form a small posterior fontanelle, and a larger, diamond-shaped anterior fontanelle. These regions allow for the skull to pass the birth canal and for later growth. The fontanelles gradually ossify, whereby the posterior fontanelle usually closes by eight weeks and the anterior fontanelle by the 9th to 16th month of age. Large fontanelles are diagnosed if the fontanelles are larger than age-dependent norms. Evidence: PCS. Onset: Congenital onset (HP:0003577). (PMID:16722536)
- Attenuation of retinal blood vessels (HP:0007843): Narrowing of the retinal blood vessels, both arterioles and venules. Evidence: PCS. Frequency: 3/3. (PMID:12563048)
- Agenesis of cerebellar vermis (HP:0002335): Congenital absence of the vermis of cerebellum. Evidence: TAS. (OMIM:610377)
- Posteriorly rotated ears (HP:0000358): A type of abnormal location of the ears in which the position of the ears is characterized by posterior rotation (the superior part of the ears is rotated towards the back of the head, and the inferior part of the ears towards the front). Evidence: PCS. (PMID:16722536)
- Elevated erythrocyte sedimentation rate (HP:0003565): An increased erythrocyte sedimentation rate (ESR). The ESR is a test that measures the distance that erythrocytes have fallen after one hour in a vertical column of anticoagulated blood under the influence of gravity. The ESR is a nonspecific finding. An elevation may indicate inflammation or may be caused by any condition that elevates fibrinogen. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Kyphoscoliosis (HP:0002751): An abnormal curvature of the spine in both a coronal (lateral) and sagittal (back-to-front) plane. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Downslanted palpebral fissures (HP:0000494): The palpebral fissure inclination is more than two standard deviations below the mean. Evidence: PCS. (PMID:16722536)
- Microcephaly (HP:0000252): Head circumference below 2 standard deviations below the mean for age and gender. Evidence: PCS. Frequency: 2/3. (PMID:8352861)
- Dysarthria (HP:0001260): Dysarthric speech is a general description referring to a neurological speech disorder characterized by poor articulation. Depending on the involved neurological structures, dysarthria may be further classified as spastic, flaccid, ataxic, hyperkinetic and hypokinetic, or mixed. Evidence: PCS. Frequency: 1/3. (PMID:12563048)
- Global developmental delay (HP:0001263): A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age. Evidence: PCS. Frequency: 16/16. (PMID:12563048;PMID:8352861)
- Progressive cerebellar ataxia (HP:0002073). Evidence: TAS. Onset: Childhood onset (HP:0011463). (OMIM:610377)
- Elevated urinary D-glyceric acid level (HP:6000606): The amount of D-glyceric acid in the urine, normalized for urine concentration, is above the upper limit of normal. Evidence: TAS. (OMIM:610377)
- Nuclear cataract (HP:0100018): A nuclear cataract is an opacity or clouding that develops in the lens nucleus. That is, a nuclear cataract is one that is located in the center of the lens. The nucleus tends to darken changing from clear to yellow and sometimes brown. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Arthralgia (HP:0002829): Joint pain. Evidence: PCS. (PMID:12563048)
- Edema (HP:0000969): An abnormal accumulation of fluid beneath the skin, or in one or more cavities of the body. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- 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:16835861)
- Fluctuating splenomegaly (HP:0006268): Intermittently increased size of the spleen. Evidence: TAS. (OMIM:610377)
- Low-set ears (HP:0000369): Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear. Evidence: PCS. (PMID:16722536)
- Triangular face (HP:0000325): Facial contour, as viewed from the front, triangular in shape, with breadth at the temples and tapering to a narrow chin. Evidence: PCS. Frequency: 2/3. (PMID:8352861)
- Increased total leukocyte count (HP:0001974): An abnormal increase in the number of leukocytes in the blood. Evidence: PCS. Frequency: 3/3. (PMID:12563048)
- 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: 3/3. (PMID:12563048)
- Failure to thrive (HP:0001508): Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm. Evidence: PCS. (PMID:16722536)
- Recurrent infections (HP:0002719): Increased susceptibility to infections as manifested by repeated bouts of infection. Evidence: PCS. Frequency: 3/3. (PMID:8352861)
- Anemia (HP:0001903): A reduction in erythrocytes volume or hemoglobin concentration. Evidence: PCS. Frequency: 3/3. (PMID:8352861)
- Normocytic hypoplastic anemia (HP:0004819): A type of hypoplastic anemia in which the erythrocytes have a normal cell volume (the mean corpuscular volume is within normal limits). Evidence: PCS. (PMID:16722536)
- Lymphadenopathy (HP:0002716): Enlargement (swelling) of a lymph node. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Increased circulating lactate dehydrogenase concentration (HP:0025435): An elevated level of the enzyme lactate dehydrogenase in the blood circulation. Evidence: PCS. Frequency: 1/1. (PMID:2850914)
- Elevated circulating hepatic transaminase concentration (HP:0002910): Elevations of the levels of SGOT and SGPT in the serum. SGOT (serum glutamic oxaloacetic transaminase) and SGPT (serum glutamic pyruvic transaminase) are transaminases primarily found in the liver and heart and are released into the bloodstream as the result of liver or heart damage. SGOT and SGPT are used clinically mainly as markers of liver damage. Evidence: PCS. Frequency: 1/1. (PMID:2850914)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Increased circulating IgD concentration (HP:0410246): An abnormally increased level of immunoglobulin D in blood. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: PCS. (PMID:8352861)
- Underdeveloped nasal alae (HP:0000430): Thinned, deficient, or excessively arched ala nasi. Evidence: PCS. Frequency: 2/3. (PMID:8352861)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Blue sclerae (HP:0000592): An abnormal bluish coloration of the sclera. Evidence: PCS. (PMID:16722536)
- Elevated circulating C-reactive protein concentration (HP:0011227): The concentration of C-reactive protein in the blood circulation is above the upper limit of normal. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Morbilliform rash (HP:0012282): An exanthema consisting of widespread pink-to-red macules (flat spots of 2-10 mm in diameter) or papules (red bumps) that blanch with pressure. The macules and papules may cluster and merge to form sheets over several days. Evidence: PCS. (PMID:16722536)
- Fluctuating hepatomegaly (HP:0006564): Intermittently increased size of the liver. Evidence: TAS. (OMIM:610377)
- Skin rash (HP:0000988): A red eruption of the skin. Evidence: PCS. Frequency: 2/3. (PMID:12563048)
- Dolichocephaly (HP:0000268): An abnormality of skull shape characterized by a increased anterior-posterior diameter, i.e., an increased antero-posterior dimension of the skull. Cephalic index less than 76%. Alternatively, an apparently increased antero-posterior length of the head compared to width. Often due to premature closure of the sagittal suture. Evidence: PCS. (PMID:16722536)
- Optic disc pallor (HP:0000543): A pale yellow discoloration of the optic disc (the area of the optic nerve head in the retina). The optic disc normally has a pinkish hue with a central yellowish depression. Evidence: PCS. Frequency: 1/3. (PMID:12563048)
- Hepatosplenomegaly (HP:0001433): Simultaneous enlargement of the liver and spleen. Evidence: PCS. Frequency: 5/6. (PMID:12563048;PMID:8352861)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: PCS. (PMID:16722536)
These phenotypes are associated with the disease mevalonic aciduria (OMIM:610377).