SNP Shot: Genomic Insights

CLPB deficiency is a rare genetic condition marked by neurological issues and neutropenia, a deficiency in infection-fighting white blood cells. The symptoms and signs manifest in early childhood, with varying degrees of severity across individuals.

In the most severe cases, CLPB deficiency symptoms are evident in infancy or even at birth. Affected infants exhibit significant neurological problems, including an exaggerated startle response (hyperekplexia) to stimuli like loud noises, impaired movement, either reduced (hypotonia) or increased (hypertonia) muscle tone, swallowing difficulties, breathing problems, and recurring seizures (epilepsy). They may also experience movement disorders like ataxia (coordination problems), dystonia (involuntary muscle tensing), or dyskinesia (uncontrolled body movements). Furthermore, severe neutropenia leads to recurrent, life-threatening infections. These individuals face a heightened risk of developing myelodysplastic syndrome (a blood cell disorder) or leukemia (blood cancer). Due to the severity of these health complications, infants with the most severe form usually survive for only a few weeks or months.

Moderately affected individuals experience neurological problems similar to the severe cases, but to a lesser degree. These include hypotonia, spasticity (muscle stiffness), and movement abnormalities. Other features of moderate CLPB deficiency include epilepsy and mild to severe intellectual disability. Neutropenia in these individuals can cause recurrent infections, although they are generally not life-threatening.

Mildly affected individuals may not exhibit any neurological problems. While they still have neutropenia, it doesn't increase their risk of infections. Some individuals with mild CLPB deficiency may develop nephrocalcinosis (calcium deposits in the kidneys) or renal cysts (kidney cysts).

Cataracts, clouding of the eye lenses, are common in individuals with mild, moderate, or severe CLPB deficiency, either present at birth (congenital) or developing in infancy.

CLPB deficiency is associated with elevated levels of 3-methylglutaconic acid in the urine (3-methylglutaconic aciduria). This abnormality, useful for diagnosis, doesn't seem to directly cause any health issues.

Inheritance:

The condition follows an autosomal recessive inheritance pattern. This means that for the condition to manifest, an individual must inherit a mutated copy of the CLPB gene from both parents. The parents, who each carry one copy of the mutated gene, are typically asymptomatic (do not show signs or symptoms of the condition).