NCBI updates clinical reference for HEXA enzyme disorders
The National Center for Biotechnology Information published an updated clinical summary of HEXA disorders, a continuum of conditions caused by deficient beta-hexosaminidase A enzyme activity. Authors Toro, Shirvan, and Tifft describe how the phenotype depends on residual HEX A enzyme levels. Without functioning HEX A, GM2 ganglioside accumulates in brain and nerve cell lysosomes. Classic Tay-Sachs disease begins at three to six months with progressive weakness and loss of motor skills. Affected children show decreased visual attentiveness and exaggerated startle response. A cherry-red spot appears on the retina. Developmental plateau occurs after eight to ten months, followed by skill loss. Seizures typically start by 12 months, with further deterioration in the second year and death between ages two and five, sometimes extending to seven years. Subacute juvenile onset occurs at age two with abnormal gait or speech problems. Loss of acquired skills and cognitive decline follow. Spasticity, difficulty swallowing, and seizures emerge by the end of the first decade, with death in the second decade, usually from aspiration. Late-onset forms present in teens or young adults with slowly progressive neurologic symptoms including lower-extremity weakness, muscle wasting, speech difficulties, poor coordination, tremor, mild spasticity or dystonia, and psychiatric manifestations including acute psychosis. Clinical variability occurs even within families for both juvenile and late-onset forms. Diagnosis requires abnormally low HEX A enzyme activity and identification of biallelic HEXA pathogenic variants through molecular genetic testing. Targeted analysis for certain pathogenic variants can be performed first in individuals of specific ethnicity, such as French Canadian or Ashkenazi Jewish populations.
The updated reference gives clinicians detailed clinical markers to recognize HEXA disorders across different age groups and severity levels.
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