Histidinaemia. Part II: Impact; a retrospective study

Area of Science:

• Medical Genetics
• Neurology
• Developmental Pediatrics

Background:

• Histidinaemia is an inborn error of histidine metabolism.
• Previous studies suggested a link between histidinaemia and adverse neurodevelopmental outcomes.
• The actual clinical spectrum and prevalence of the histidinaemia phenotype remain incompletely understood.

Purpose of the Study:

• To retrospectively analyze the impact of histidinaemia on human development and health.
• To characterize the central nervous system (CNS) phenotype in individuals with histidinaemia.
• To estimate the proportion of histidinaemia cases exhibiting a disadaptive CNS phenotype.

Main Methods:

• Retrospective review of 42 articles published between 1961 and 1977.
• Analysis of data from 43 probands and 26 siblings diagnosed with histidinaemia.
• Examination of reported clinical features, including neurological and behavioral outcomes, and cognitive assessments (IQ scores).

Main Results:

• A significant proportion (79%) of probands exhibited a disadaptive CNS phenotype, including intellectual disability, speech impairment, seizures, behavioral issues, and learning disorders.
• Approximately half of the affected siblings presented with similar CNS phenotypes.
• No correlation was found between blood histidine levels and the presence or severity of the CNS phenotype.

Conclusions:

• While a substantial percentage of reported histidinaemia cases show CNS abnormalities, these may represent a small fraction of all individuals with the condition.
• The findings suggest that the histidinaemia phenotype is not consistently disadaptive in the general population.
• Further research is needed to fully elucidate the genotype-phenotype correlations and long-term health implications of histidinaemia.