Severity in phenotypic expression of homozygous sickle cell disease (Hb.SS)--does hypermelanotic or hypomelanotic skin status of affected patients play a role?

摘要

Abnormal hemoglobin distribution on global map, of which hemoglobin S (Hb.S) accounted for about 80% of the disorders resulting from them are more prevalent in the tropics and sub-tropics. Homozygous sickle cell disease (Hb.SS) is the most common and most severe form of sickle cell disease (SCD) in phenotypic expression. The prevalence and severity in phenotypic expression of SCD had been noted to decrease farther away from the equatorial region, with prevalence rate of sickle cell trait of about 2% and less than 1% in North African coast and South Africa, respectively, compared to about 10-40% in the equatorial region. Controlling for human migration, the distribution of prevalence and severity of SCD tend to correspond with the degree of pigmentation of skin color on global map with areas of hyperpigmentation having the likelihood of higher prevalence and severity, while areas of hypopigmentation are characterized by the reverse. This distribution had been observed to correspond with skin color variation on global map based on Von Luschan's chromatic scale. Empirical observation had also shown that individual homozygous SCD patients who are lighter in skin color tend to manifest a less severe phenotypic expression of the disease condition when compared to those with darker skin color using the yard stick of frequency in sickle cell crises. The hypothesis is; would hypermelanotic or hypomelanotic skin status of individual homozygous SCD patient, if measured objectively by assessing the types and quantity of melanin in individual patient, influence the severity in phenotypic expression of SCD in affected patients. Oculocutaneous albinism (OCA) which is characterized by hypomelanosis is an inherited autosomal recessive disorder like SCD. OCA is also common in the tropics and sub-tropics like SCD. It had been reported that OCA does occur co-morbidly with homozygous SCD. Comparing a group of patients with co-morbid OCA and homozygous SCD with another group with SCD, who do not have OCA on severity of phenotypic expression of SCD could provide a feasible means of testing the hypothesis. If future carefully controlled studies confirm the hypothesis of influence of hypermelanotic or hypomelanotic skin status of the individual patients on severity in phenotypic expression of homozygous SCD, genetic and pharmacological interventions aimed at regulation of melanin production may play a role in alleviating the severity in phenotypic expression of SCD in affected patients.