الفهرس 
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Abstract
Inborn errors of metabolism (IEM) are a heterogeneous group of genetic disorders that cause dysfunction of an enzyme or transporter involved in cellular metabolism, inborn errors were thought to be rare, occurring in less than 1 per 100,000 live births and to only present during infancy or early childhood. We now know that this prevalence is an underestimate, and that IEM present much more often than previously thought.
IMDs can be divided into three practical diagnostic groups according to their path-biological mechanisms: (1) cellular intoxication; (2) energy metabolism deficiency; and (3) defects of degradation or synthesis of complex molecules.
Some such conditions of IEM present primarily with neurological or psychiatric symptoms. Missing or delaying diagnosis of an IEM can have important implications. In particular, patients with a milder phenotype appear to benefit most from timely treatment, so early diagnosis is important to prevent further neurological damage.
Whereas the neurological symptoms in children with IEM often involve various types of movement disorders. Seizures, stroke, encephalopathy, developmental delay or psychiatric disorders are also frequently observed and can be important diagnostic clues.
The aim of this study was to determine the frequency of different types of inborn errors of metabolism in high risk children with clinical sign and symptoms suggestive to inherited metabolic diseases and to spotlight the neurological and psychiatric disturbances that may occur in children with inherited metabolic diseases.
Summary
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During the study 1700 cases suspected with IEM, included 1061male (62.4%) and 639 female (37.6%), with positive consanguinity in 64.6% of them, 19.6% of patients had history of other sibling death and about 1% had family history of IEM.
IEM was proved in 105 patients (6.2% of suspected cases). Aminoacidopathy was the most frequently diagnosed family of IEM,
For detection of neurological or psychiatric disturbances that can be observed in children with inherited metabolic diseases. All diagnosed patients with inborn errors of metabolism 154 patients, their ages ranged from 1 week to 16 years divided to two main groups and other IEM collected in third group.
group 1: It included 90 children diagnosed to have inborn errors of protein metabolism.
group 2: included 35children with carbohydrate inborn error of metabolism (glycogen storage disease).
group 3: included 29 children.
All the studied children were subjected to: Detailed history taking, thorough clinical examination and Laboratory investigations, Electroencephalogram (EEG), Magnetic Resonance Imaging.
Amino acid disorders accounted for the largest proportion of cases. The most common aminoacidemia was PKU (44.4%)
Our study showed that, there were no significant differences between protein and carbohydrate IEM groups as regarding demographic data such as regard age, sex, residence, mode of delivery, age of onset and family history of metabolic diseases.
The percentages of positive consanguinity were 58.9% in protein IEM group and 82.9% in carbohydrate IEM group.
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As regarding neurological clinical presentation in proteins IEM group, 23.3% of patients presented with affection of conscious level (lethargy, irritability, behavior disturbances or coma), followed by global developmental delay in 22.2%. In carbohydrates IEM group the most clinical presentation was seizures in 25.7% and DCL in 14.3%.
Our studied showed that 25.6% of patients with inborn errors of protein metabolism had delayed motor development, 36.7% of patients had low IQ <70 and 5.6% of them had borderline IQ (70-79) and 32.2% of them had delayed speech. In carbohydrate IEM group all patients were normal regarding language and motor developmental while 34.3% of patients had borderline IQ (70-79).
Abnormal MRI findings present in 55.6% of patients in protein IEM group. In carbohydrate IEM group 34.3% had abnormal MRI findings
Abnormal EEG findings present in 12.2% of patients in protein IEM group and in carbohydrate IEM group 2.9% (one patient) had abnormal EEG
EMG and nerve conduction was done for hypotonic patientsand found that 1.1% of them (one methylmalonic patient) were abnormal with demyelinating neuropathy. While in carbohydrate IEM group, EMG in 57% of patients was normal and 34.3% were abnormal with picture of myopathy.
The third group in our study included patients with different categories. Positive consanguinity presents in 65.5% and positive family history of similar condition found in 13.8%.
The most clinical presentations were GDD in 34.5%, seizures in 27.6%, affection of conscious level in 6.9%, 75.9% of them had MRI abnormalities. 17.2% had abnormal EEG. Electromyographic study
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was done in six patients complaining of hypotonia and found that 16.9% were abnormal with demyelinating neuropathy at both lower limbs.
Collectively, neurological presentation was found in 119 patients of all 154 patients diagnosed with IEM. The most common presentations were global developmental delay and affection of conscious level followed by convulsions, ADHD, delayed mentality, abnormal movement and autism.
Our study showed that there was significant relation between age of onset of inborn errors disease and patient’s motor and mental development, with positive significant correlation between age of onset and patient’s motor development, while there was negative significant correlation between age of onset and patient’s mentality.
We have found a significant number of positive cases in our series of patients, establishing the fact that IEM is quite prevalent in our population, though remain under diagnosed. IEM represent a significant cause for many acute and chronic neurological and psychiatric symptoms in children, inborn errors of metabolism must be suspected whenever a patient presents metabolic disturbances or neurological manifestations without a determined cause. Investigations for IEM should be done routinely in NICU for neonates with suspected presentations, until nationwide newborn screening can be applied in Egypt.