- Lethargy (HP:0001254): A state of fatigue, either physical or mental slowness and sluggishness, with difficulties in initiating or performing simple tasks. Distinguished from apathy which implies indifference and a lack of desire or interest in the task. A person with lethargy may have the desire, but not the energy to engage in personal or socially relevant tasks. Evidence: IEA. (OMIM:253260)
- Organic aciduria (HP:0001992): Excretion of non-amino organic acids in urine. Evidence: PCS. Frequency: 25/29. (PMID:4073853)
- Alopecia (HP:0001596): A noncongenital process of hair loss, which may progress to partial or complete baldness. Evidence: PCS. Frequency: 24/31. (PMID:4073853)
- Seizure (HP:0001250): A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain. Evidence: PCS. Frequency: 22/31. (PMID:4073853)
- Seborrheic dermatitis (HP:0001051): Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk. Evidence: IEA. (OMIM:253260)
- 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: 27/31. (PMID:4073853)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: IEA. (OMIM:253260)
- 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: 18/31. (PMID:4073853)
- Infantile onset (HP:0003593): Onset of signs or symptoms of disease between 28 days to one year of life. Evidence: PCS. (PMID:4073853)
- Diffuse cerebellar atrophy (HP:0100275): Diffuse unlocalised atrophy affecting the cerebellum. Evidence: IEA. (OMIM:253260)
- Childhood onset (HP:0011463): Onset of disease at the age of between 1 and 5 years. Evidence: PCS. (PMID:4073853)
- Hyperammonemia (HP:0001987): An increased concentration of ammonia in the blood. Evidence: PCS. Frequency: 10/31. (PMID:4073853)
- Feeding difficulties in infancy (HP:0008872): Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention. Evidence: IEA. (OMIM:253260)
- Splenomegaly (HP:0001744): Abnormal increased size of the spleen. Evidence: IEA. (OMIM:253260)
- Visual loss (HP:0000572): Loss of visual acuity (implying that vision was better at a certain time point in life). Otherwise the term reduced visual acuity should be used (or a subclass of that). Evidence: IEA. (OMIM:253260)
- Diarrhea (HP:0002014): Abnormally increased frequency (usually defined as three or more) loose or watery bowel movements a day. Evidence: IEA. (OMIM:253260)
- Decreased circulating biotinidase concentration (HP:0410145): Concentration of biotinidase in the blood circulation below the lower limit of normal. Biotidinase is an enzyme that releases biotin from biocytin, the product of biotin-dependent carboxylases degradation. Evidence: PCS. (PMID:3930842)
- Vomiting (HP:0002013): Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions. Evidence: IEA. (OMIM:253260)
- 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: 29/41. (PMID:4073853;OMIM:253260)
- Recurrent skin infections (HP:0001581): Infections of the skin that happen multiple times. Evidence: IEA. (OMIM:253260)
- Sensorineural hearing impairment (HP:0000407): A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve. Evidence: IEA. (OMIM:253260)
- Conjunctivitis (HP:0000509): Inflammation of the conjunctiva. Evidence: PCS. Frequency: 14/31. (PMID:4073853)
- Diffuse cerebral atrophy (HP:0002506): Diffuse unlocalised atrophy affecting the cerebrum. Evidence: IEA. (OMIM:253260)
- 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: IEA. (OMIM:253260)
- Optic atrophy (HP:0000648): Atrophy of the optic nerve. Optic atrophy results from the death of the retinal ganglion cell axons that comprise the optic nerve and manifesting as a pale optic nerve on fundoscopy. Evidence: PCS. Frequency: 17/31. (PMID:4073853)
- Skin rash (HP:0000988): A red eruption of the skin. Evidence: PCS. Frequency: 21/31. (PMID:4073853)
- Metabolic ketoacidosis (HP:0005979): A metabolic acidosis due to accumulation of ketone bodies generally observed in the setting of poor nutritional intake. Evidence: PCS. Frequency: 25/31. (PMID:4073853)
- Tachypnea (HP:0002789): Very rapid breathing. Evidence: PCS. Frequency: 6/31. (PMID:4073853)
- Apnea (HP:0002104): Lack of breathing with no movement of the respiratory muscles and no exchange of air in the lungs. This term refers to a disposition to have recurrent episodes of apnea rather than to a single event. Evidence: IEA. (OMIM:253260)
These phenotypes are associated with the disease biotinidase deficiency (OMIM:253260).