- Poor head control (HP:0002421): Difficulty to maintain correct position of the head while standing or sitting. Infant head lag is observed when the head seems to flop around or lags posteriorly behind the trunk. Several articles have maintained that head lag should be absent by age 3 to 4 months. Evidence: TAS. (OMIM:613839)
- Pallor (HP:0000980): Abnormally pale skin. Evidence: TAS. (OMIM:613839)
- Generalized non-motor (absence) seizure (HP:0002121): A generalized non-motor (absence) seizure is a type of a type of dialeptic seizure that is of electrographically generalized onset. It is a generalized seizure characterized by an interruption of activities, a blank stare, and usually the person will be unresponsive when spoken to. Any ictal motor phenomena are minor in comparison to these non-motor features. Evidence: TAS. (OMIM:613839)
- 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: TAS. (OMIM:613839)
- 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: TAS. (OMIM:613839)
- Hepatomegaly (HP:0002240): Abnormally increased size of the liver. Evidence: TAS. (OMIM:613839)
- Delayed myelination (HP:0012448): Delayed myelination. Evidence: TAS. (OMIM:613839)
- Generalized hypotonia (HP:0001290): Generalized muscular hypotonia (abnormally low muscle tone). Evidence: TAS. (OMIM:613839)
- Decreased CSF 5-methyltetrahydrofolate concentration (HP:0012446): A reduced concentration of 5-methyltetrahydrofolate(2-) in the cerebrospinal fluid (CSF). 5-methyltetrahydrofolate is the active folate metabolite. Evidence: PCS. Frequency: 2/2. (PMID:21310277)
- Megaloblastic anemia (HP:0001889): Anemia characterized by the presence of erythroblasts that are larger than normal (megaloblasts). Evidence: PCS. Frequency: 2/3. (PMID:21310277)
- Increased circulating lactate dehydrogenase concentration (HP:0025435): An elevated level of the enzyme lactate dehydrogenase in the blood circulation. Evidence: PCS. Frequency: 1/3. (PMID:21310277)
- Jaundice (HP:0000952): Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream. Evidence: TAS. (OMIM:613839)
- Cerebral atrophy (HP:0002059): Atrophy (wasting, decrease in size of cells or tissue) affecting the cerebrum. Evidence: TAS. (OMIM:613839)
- Juvenile onset (HP:0003621): Onset of signs or symptoms of disease between the age of 5 and 15 years. Evidence: PCS. Frequency: 1/3. (PMID:21310277)
- Cerebellar hypoplasia (HP:0001321): Cerebellar hypoplasia is a descriptive term implying a cerebellum with a reduced volume, but a normal shape and is stable over time. Evidence: IEA. (OMIM:613839)
- Eyelid myoclonus (HP:0025097): Marked, involuntary jerking of the eyelids. Evidence: TAS. (OMIM:613839)
- Feeding difficulties (HP:0011968): Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it. Evidence: TAS. (OMIM:613839)
- 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: TAS. (OMIM:613839)
- Secondary microcephaly (HP:0005484): Head circumference which falls below 2 standard deviations below the mean for age and gender because of insufficient head growth after birth. Evidence: TAS. (OMIM:613839)
- Absence seizure with eyelid myoclonia (HP:0011149): An absence with eyelid myoclonia seizure is a type of generalized non-motor (absence) seizure characterized by forced upward jerking of the eyelids during an absence seizure. Evidence: PCS. Frequency: 2/3. (PMID:21310277)
- Abnormal circulating folate concentration (HP:0040087): Any deviation from the normal concentration of folate in the blood circulation. Evidence: PCS. Frequency: 0/3. (PMID:21310277)
- 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:21310277)
- Increased mean corpuscular volume (HP:0005518): Larger than normal size of erythrocytes. Evidence: PCS. Frequency: 3/3. (PMID:21310277)
- Thrombocytopenia (HP:0001873): A reduction in the number of circulating thrombocytes. Evidence: TAS. (OMIM:613839)
- Pancytopenia (HP:0001876): An abnormal reduction in numbers of all blood cell types (red blood cells, white blood cells, and platelets). Evidence: TAS. (OMIM:613839)
These phenotypes are associated with the disease constitutional megaloblastic anemia with severe neurologic disease (OMIM:613839).