Demographic and clinical features of glutaric acidemia type 1; a high frequency among isolates in Upper Egypt

Abstract

Objective: Glutaric acidemia type 1 (GA1) was thought to be a rare disorder in Arab countries. Recently, a relatively large number of patients with GA1 have been detected in Egypt. The aim of this work was to: (1) find out the commonest clinical characteristics of the disease among Egyptians presenting with GA1; (2) delineate the demographic factors that may lead to a high prevalence of GA1 among Egyptians; (3) Recommend the most suitable strategy to screen for the disease.
Patients and methods: The study included all patients with GA1 who presented at The Genetics Unit, Ain Shams University Hospital (GUASH) during the last three years. The information about patients with GA1 including the epidemiological and clinical data was obtained retrospectively from patients’ files.
Results: The authors surveyed data of 26 patients in 23 families who were personally examined and the diagnosis was confirmed by laboratory data. The mean age of onset of symptoms was 5.8± 2.2 months: the mean delay in establishing the diagnosis was 11.73± 13.97 months. At the onset of symptoms, macrocephaly (85%) was the commonest feature of GAI followed by dystonia (69%), and persistent convulsions (50%). Onset of symptoms occurred during an acute febrile illness in 68% of patients, which was associated with the worst forms of dystonia (X2 = 12.5, p =0.14). The frequency of affected Christian families among all affected families was 43%, which is significantly higher than that expected of the Christian minority in Egypt (6–15%). There has been no significant increase in consanguinity among those Christian families (F = 0.014204) pointing to a high gene frequency of GA1 in isolated areas in Upper Egypt.
Recommendation: In the absence of mass newborn screening program, continuous Health Education program should be implemented to promote detection of early signs of GA1 such as macrocephaly before the occurrence of acute crisis of encephalopathy especially in families with history of similar patients. We recommend that a nationwide program of extended tandem mass screening should cover all newborns in Egypt to promote early detection of patients with GA1 and to avoid the severe consequences of the delay in diagnosis.

Keywords: Glutaric acidemia type 1; Inborn errors of metabolism; Egypt; Genetics; Consanguinity; Newborn screening