ABSTRACT
BACKGROUND: X-linked adrenoleukodystrophy is a genetic disease affecting the degradation of very long chain fatty acids. This study aims to describe the clinical phenotype and biochemical feature of Tunisian patients; it also seeks to describe recognition of pattern analysis on the level of very long chain fatty acids in plasma for the visual discrimination of X-linked patients from a healthy group. METHODS: During the last 21 years, 19 patients were diagnosed with X-linked adrenoleukodystrophy based on the clinical features combined with the area percentage of hexacosanoic acid (C26:0) as well as the ratio of C26:0 and lignoceric acid (C24:0) relative to behenic acid (C22:0) by gas chromatography. For the biochemical diagnosis of X-ALD with better accuracy, it has been desired to transform the numerical values of these biochemical markers into visually discriminating patterns. RESULTS: The clinical features of 19 patients aged between 4 to 47 years were classified into cerebral form (57.8%), adrenomyeloneuropathic (26.3%), and a few patients were asymptomatic. The ratio C24:0/C22:0 ranged from 1.12 to 2.41 (normal value: 0.46 - 0.9) and C26:0/C22:0 ratio ranged from 0.03 to 0.36 (normal value: 0.003 - 0.009). The concentration of fatty acids with 22 or more carbons in body fluid did not change with age in control subjects and patients. For the visual diagnostic of patients, the Scatter plot was a reliable method for the diagnostic patterns of very long chain fatty acids of patients with X-linked adrenoleukodystrophy disorders. CONCLUSIONS: The incidence of X-linked adrenoleukodystrophy disorders is under diagnosed in Tunisia. The diagnosis was confirmed by enzymatic activity study and molecular analysis but the analysis of very long chain fatty acids by gas chromatography remains a reliable tool for the diagnosis and early initiation of the treatment.
Subject(s)
Adrenoleukodystrophy/diagnosis , Adrenoleukodystrophy/epidemiology , Adolescent , Adrenoleukodystrophy/classification , Adult , Child , Child, Preschool , Chromatography, Gas , Family Health , Fatty Acids/analysis , Female , Humans , Male , Middle Aged , Pattern Recognition, Automated , Phenotype , Reproducibility of Results , Retrospective Studies , Tunisia/epidemiologyABSTRACT
BACKGROUND: Hereditary tyrosinemia type 1 (HT1) is an autosomal recessive disease caused by a defect of fumarylacetoacetate hydrolase. This study aimed to estimate the prevalence of HT1 in Tunisia and report its clinical, biochemical and genetic features. METHODS: During the last 25 years, 69 patients were diagnosed with HT1 based on clinical features and increased succinylacetone (SA) in blood and urine. SA was detected by GC-MS after oximation and quantified by a spectrophotometric method. Nine prenatal diagnoses for HT1 have been done and nine unrelated patients were screened for the hotspot IVS6-1(G-T) mutation using PCR. RESULTS: Using the Hardy-Weinberg formula, the incidence of HT1 was estimated at 1/14804 births in Tunisia. According to clinical form, 21 patients (30%) had the acute form and 48 patients (70%) had the chronic form. Mean plasma and urine SA were higher in the acute form (24 and 193 µmol/L vs. 9 and 90 µmol/L, respectively). Diagnosis of HT1 was done for 4 fetuses. The hotspot IVS6-1(G-T) mutation was found in six of nine explored patients. CONCLUSIONS: The incidence of HT1 is relatively high in Tunisia with a predominance of the chronic form. It is important to diagnose the disease as early as possible to prevent unfavorable issues. Prenatal diagnosis should be recommended to minimize the recurrence of the disease.
