CLPB deficiency

Also known as: 3-methylglutaconic aciduria-cataract-neurologic involvement-neutropenia syndrome; 3-methylglutaconic aciduria type 7; 3-methylglutaconic aciduria type VII; 3-methylglutaconic aciduria with cataracts, neurologic involvement and neutropenia; MEGCANN; MGA7; MGCA7

Definition

Genetics Home Reference

CLPB deficiency is a rare disorder characterized by neurological problems and a shortage of infection-fighting white blood cells (neutropenia). Signs and symptoms of the condition develop by early childhood, and their severity varies widely among affected individuals.

In the most severely affected individuals, features of CLPB deficiency are apparent in infancy and sometimes at birth. Affected babies have serious neurological problems, which can include an exaggerated startle reaction (hyperekplexia) to unexpected stimuli such as loud noises, reduced movement, muscle tone that is either decreased (hypotonia) or increased (hypertonia), swallowing problems, difficulty breathing, and recurrent seizures (epilepsy). These babies may also have movement abnormalities, such as difficulty coordinating movements (ataxia), involuntary tensing of the muscles (dystonia), or uncontrolled movements of the body (dyskinesia). In addition, these babies have recurrent, life-threatening infections due to severe neutropenia. Affected individuals are at risk of developing a blood cell disorder called myelodysplastic syndrome or a form of blood cancer called leukemia. Because of their severe health problems, affected infants usually live only a few weeks or months.

Moderately affected individuals have neurological problems similar to those described above, although they are less severe. They include hypotonia, muscle stiffness (spasticity), and movement abnormalities. Other features of moderate CLPB deficiency include epilepsy and mild to severe intellectual disability. Neutropenia in these individuals can lead to recurrent infections, although they are not life-threatening.

Mildly affected individuals have no neurological problems, and although they have neutropenia, it does not increase the risk of infections. Some people with mild CLPB deficiency develop deposits of calcium in the kidneys (nephrocalcinosis) or kidney (renal) cysts.

Many people with mild, moderate, or severe CLPB deficiency have clouding of the lenses of the eyes (cataracts) from birth (congenital) or beginning in infancy.

CLPB deficiency is associated with increased levels of a substance called 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria). This abnormality, which provides a clue to the diagnosis, does not appear to cause any health problems.

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Symptoms

Medical Term Other Names Description
Cataract Lens opacities, Lens opacity, Cloudy lens [more] A cataract is an opacity or clouding that develops in the crystalline lens of the eye or in its capsule.
Aciduria Excretion of urine with an acid pH.
Hypertonia Increased muscle tone, Hypertonicity, Muscle hypertonia [more] A condition in which there is increased muscle tone so that arms or legs, for example, are stiff and difficult to move.
Neutropenia Peripheral neutropenia, Low blood neutrophil count, Low neutrophil count [more] An abnormally low number of neutrophils in the peripheral blood.
Respiratory distress Respiratory difficulties, Shortness of breath, Short of breath, Difficulty breathing, Breathing difficulties [more] Difficulty in breathing. The physical presentation of respiratory distress is generally referred to as labored breathing, while the sensation of respiratory distress is called shortness of breath or dyspnea.
Myelodysplasia Myelodysplastic syndrome, Hypoplastic myelodysplasia Clonal hematopoietic stem cell disorders characterized by dysplasia (ineffective production) in one or more hematopoietic cell lineages, leading to anemia and cytopenia.
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.
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).
Spasticity Muscle spasticity, Muscular spasticity A motor disorder characterized by a velocity-dependent increase in tonic stretch reflexes with increased muscle tone, exaggerated (hyperexcitable) tendon reflexes.
Dyskinesia Dyskinesis A movement disorder which consists of effects including diminished voluntary movements and the presence of involuntary movements.
Recurrent infections Susceptibility to infection, Frequent infections, Predisposition to infections, Increased frequency of infection [more] Increased susceptibility to infections.
Muscle stiffness A condition in which muscles cannot be moved quickly without accompanying pain or spasm.
Generalized hypotonia Generalized muscular hypotonia, Decreased muscle tone, Low muscle tone, Hypotonia [more] Generalized muscular hypotonia (abnormally low muscle tone).
Exaggerated startle response Increased startle response, Hyperekplexia, Exaggerated acoustic startle response [more] An exaggerated startle reaction in response to a sudden unexpected visual or acoustic stimulus, or a quick movement near the face.
Nephrocalcinosis Increased calcium level in kidney Nephrocalcinosis is the deposition of calcium salts in renal parenchyma.
Dystonia Dystonic movements, Dystonic disease An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.
Leukemia Blood cancer A cancer of the blood and bone marrow characterized by an abnormal proliferation of leukocytes.
3-Methylglutaconic aciduria

Other Classifiers and IDs