Phosphoglycerate dehydrogenase deficiency

Also known as: 3-PGDH deficiency, 3-phosphoglycerate dehydrogenase deficiency, PHGDH deficiency

Definition

Genetics Home Reference

Phosphoglycerate dehydrogenase deficiency is a condition characterized by an unusually small head size (microcephaly); impaired development of physical reactions, movements, and speech (psychomotor retardation); and recurrent seizures (epilepsy). Different types of phosphoglycerate dehydrogenase deficiency have been described; they are distinguished by their severity and the age at which symptoms first begin. Most affected individuals have the infantile form, which is the most severe form, and are affected from infancy. Symptoms of the juvenile and adult types appear later in life; these types are very rare.

In phosphoglycerate dehydrogenase deficiency there is a progressive loss of brain cells leading to a loss of brain tissue (brain atrophy), specifically affecting the fatty tissue known as myelin that surrounds nerve cells (hypomyelination). Frequently, the tissue that connects the two halves of the brain (corpus callosum) is small and thin, and the fluid-filled cavities (ventricles) near the center of the brain are enlarged. Because development of the brain is disrupted, the head does not grow at the same rate as the body, so it appears that the head is getting smaller as the body grows (progressive microcephaly). Poor brain growth leads to an inability to achieve many developmental milestones such as sitting unsupported and speaking. Many affected infants also have difficulty feeding.

The seizures in phosphoglycerate dehydrogenase deficiency can vary in type. Recurrent muscle contractions called infantile spasms are typical early in the disorder. Without early treatment, seizures may progress to tonic-clonic seizures, which involve a loss of consciousness, muscle rigidity, and convulsions; myoclonic seizures, which involve rapid, uncontrolled muscle jerks; or drop attacks, which are sudden episodes of weak muscle tone.

Individuals with the infantile form of phosphoglycerate dehydrogenase deficiency develop many of the features described above. Individuals with the juvenile form typically have epilepsy as well as mild developmental delay and intellectual disability. Only one case of the adult form has been reported; signs and symptoms began in mid-adulthood and included mild intellectual disability; difficulty coordinating movements (ataxia); and numbness, tingling, and pain in the arms and legs (sensory neuropathy).

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Orphanet

3-Phosphoglycerate dehydrogenase deficiency (3-PGDH deficiency) is an autosomal recessive form of serine deficiency syndrome (see this term) characterized clinically in the few reported cases by congenital microcephaly, psychomotor retardation and intractable seizures in the infantile form and by absence seizures, moderate developmental delay and behavioral disorders in the juvenile form

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Symptoms

Medical Term Other Names Description
Seizures Epilepsy Seizures are an intermittent abnormality of the central nervous system due to a sudden, excessive, disorderly discharge of cerebral neurons and characterized clinically by some combination of disturbance of sensation, loss of consciousness, impairment of psychic function, or convulsive movements. The term epilepsy is used to describe chronic, recurrent seizures.
Ataxia Cerebellar ataxia 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- oder overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).
Generalized myoclonic seizures Myoclonic epilepsy, progressive, Myoclonic seizures, Myoclonus seizures [more] Seizures with sudden, brief (< 100 msec) involuntary single or multiple contraction(s) of muscles(s) or muscle groups of variable topography (axial, proximal limb, distal).
Atonic seizures drop attacks, Sudden loss of muscle tone, drop seizures, Hypotonic seizures, astatic seizures [more] Seizures characterized by a sudden loss or diminution of muscle tone, which may be fragmentary, confined to a segment (limb, jaw, head), or massive, leading to a slumping to the ground .
Progressive microcephaly Microcephaly, postnatal, progressive, Progressively abnormally small cranium, Progressively abnormally small skull [more] Progressive microcephaly is diagnosed when the head circumference falls progressively behind age- and gender-dependent norms.
Microcephaly small cranium, Decreased circumference of cranium, Small head, Small skull, Small head circumference, Reduced head circumference, Decreased size of cranium, Decreased size of skull, Abnormally small skull, Decreased size of head, Abnormally small cranium, small calvarium, Abnormally small head [more] Occipito-frontal (head) circumference (OFC) less than -3 standard deviations compared to appropriate, age matched, normal standards (Ross JJ, Frias JL 1977, PMID:9683597). Alternatively, decreased size of the cranium.
Pain An unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.
Loss of consciousness Passing out
Infantile spasms Infantile spasms represent a subset of "epileptic spasms". Infantile Spasms are epileptic spasms starting in the first year of life (infancy).
Paresthesia Tingling, Pins and needles feeling Abnormal sensations such as tingling, pricking, or numbness of the skin with no apparent physical cause.
Brain atrophy Brain degeneration, Brain wasting Partial or complete wasting (loss) of brain tissue that was once present.
CNS hypomyelination hypomyelination Reduced amount of myelin in the central nervous system resulting from defective myelinogenesis.
Absence seizures Petit mal seizures Recurrent absence seizures are generalized seizures and are characterized by a loss of consciousness, thus, are a form of dialeptic seizures.
Rigidity Muscle rigidity Continuous involuntary sustained muscle contraction. When an affected muscle is passively stretched, the degree of resistance remains constant regardless of the rate at which the muscle is stretched. This feature helps to distinguish rigidity from muscle spasticity.
Global developmental delay Psychomotor developmental delay, Psychomotor retardation, Developmental delay, Lack of psychomotor development, Cognitive delay, Delayed intellectual development, Delayed milestones, Psychomotor development deficiency, Developmental retardation, Motor and developmental delay, Developmental delay in early childhood, Retarded psychomotor development, Retarded mental development, Delayed cognitive development, Retarded development, Delayed developmental milestones, Delayed development, Psychomotor development failure, Mental and motor retardation, Psychomotor delay, Delayed psychomotor development [more] 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.
Myoclonus Jerking, Myoclonic jerks, Involuntary jerking movements [more] Very brief, involuntary random muscular contractions occurring at rest, in response to sensory stimuli, or accompanying voluntary movements.
Congenital microcephaly Small head circumference present at birth, Congenital small skull, Small cranium present at birth, Small head present at birth, Microcephaly present at birth, Congenital small head circumference, Congenital decreased head circumference, Head circumference small for gestational age, Small skull present at birth, Decreased head circumference present at birth, Congenital small head [more] Microcephaly (HP:0000252) that is present already at the time of birth.
Intellectual disability Nonprogressive intellectual disability, Poor school performance, Mental-retardation, Dull intelligence, Nonprogressive mental retardation, Mental deficiency, Mental retardation, nonspecific, Low intelligence [more] Subnormal intellectual functioning which originates during the developmental period. Intellectual disability, previously referred to as mental retardation, has been defined as an IQ score below 70.

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