Galactosialidosis is a glycoprotein storage disease; one of seven such identified diseases. Three different forms of galactosialidosis are identified, based on the age of onset of the symptoms. The early infantile form has its onset before three months of age, and infants show typical symptoms of hydrops, edema, splenohepatomegaly, cardiomegaly, impaired renal function, and skeletal changes, especially involving the spine. The late infantile form of the disease has its onset in the first few months of life, and is symptomatized by coarse facial features, hepatosplenomegaly, dysostosis multiplex, macular cherry-red spots, skeletal abnormalities, and mild mental retardation. The juvenile/adult form of the condition, however, is the most common, and has its onset around 16 years of age, although some patients only show symptoms in the fourth decade of their life. This form differs from the infantile ones by the presence of neurological problems like ataxia and seizures, and angiokeratomas. Other features remain the same.
Individuals suspected to have a glycoprotein storage disorder are asked to get their urine tested. Patients with galactosialidosis usually have a characteristic chromatographic profile of urinary oligosaccharides. A confirmation of the diagnosis can be made upon assaying the enzymatic activity of neuraminidase alpha, beta galactosidase or cathepsin A. For parents at risk for having an affected child, prenatal diagnosis is also available by way of chorionic villus sampling. There is no definite cure for the condition. Treatment is symptomatic.
Galactosialidosis results from a lack of function of the enzyme Protective Protein/Cathepsin A (PPCA). This protein forms a complex along with beta galactosidase and neuraminidase, and this complex helps in the breakdown of long sugar chains in the lysosome. Apart from its catalytic function in this complex, PPCA also serves a protective role, by protecting the other two enzymes from proteolysis. Therefore, in individuals with a loss of function of PPCA, the neuraminidase and beta galactosidase enzymes also degrade and are unable to perform their functions.
The GLB2 gene, which codes for the PPCA enzyme, spans a length of about 8.5 kb on chromosome 20. The PPCA protein is composed of 480 amino acid residues and weighs about 54 kDa. The protein is a heterodimer of a 32 kDa and a 20 kDa chains, which are linked by a disulfide bond. The protein is very similar in its structure to the yeast carboxypeptidase Y. In addition to the carboxypeptidase activity, PPCA also shows deamidase and esterase activities. The most common mutations in the GLB2 gene which result in galactosialidosis include SpDEx7 (a single base substitution at the donor splice site of exon 7), Trp65Arg, Gln49Arg, and Tyr395Cys. All four of these mutations are common among Japanese patients.
In a study to estimate the prevalence of commonly diagnosed autosomal recessive diseases in Oman from a hospital-based register in the year 1993 to 2002, Rajab et al. (2005) found that galactosialidosis was diagnosed in 9 patients, with an observed incidence of 1 in 50,000 births.
Ozand and Gascon (1992) described the clinical features and laboratory findings of seven patients with neonatal/infantile-onset galactosialidosis. The patients were all male and four of them belonged to consanguineous families. The age of onset was between birth and 7 months. Patients presented with scrotal swelling (in three), hydrocele and inguinal hernia (in one), and tonic-clonic seizures (in three). Severe neurological involvement and arrested development were seen at the 0-4 month level in all patients. Patients suffered from repeated infections and mild to moderate global brain atrophy. Other symptoms seen included dementia, myoclonus, hypotonia, spastic diplegia or quadriplegia, hazy cornea, cherry-red macula, nystagmus, optic atrophy, hepatosplenomegaly and coarse face. The neuraminidase activity in these patients ranged from 2% to 6% and beta-galactosidase varied from 0.1% to 12% of the control values. The carboxypeptidase activity was not detected in two patients, while in the remaining five patients; it ranged from below normal to 15% of the normal value. The kinetic variables could not be calculated in the first two patients because of absent activity, while in the five other patients, the Km was significantly high with normal Ki. The Vm was less than 20% in one of these five patients. No correlation was found between carboxypeptidase activity and the features of galactosialidoisis such as age of onset or progression.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Lysosomal storage disorders were the most diagnosed category of IEM in this cohort (74 out of 248 cases, 30%). Only, one case from a single family was found to have galactosialidosis, with an estimated incidence of 1 per 100,000 live births. All cases of lysosomal storage disease were confirmed by enzymatic assays. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.
Mongalgi et al. (1992) reported the case of a 4 year-old boy presenting with dysmorphic facies, hepatomegaly, splenomegaly, growth and psychomotor retardation is reported. Radiological pattern suggested a storage disease. Bone marrow differential cell count showed numerous storage cells with vacuolated lymphocytes. Enzymatic studies showed decreased beta-galactosidase and neuraminidase levels, leading to the diagnosis of galactosialidosis. This is the first Tunisian case reported, which differs from the other cases published by the presence of a Kayser-Fleischer ring.
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