Other important disorders:
Inclusion-cell (I-cell) disease (mucolipidosis II / ML II): It is caused by a mutation in the GNPTAB gene and is inherited in an autosomal recessive manner. Deficiency of the enzyme UDP-N-acetylglucosamine-1-phosphotransferase causes I-cell disease. This interferes with tagging of proteins bound for lysosomes with mannose-6-phosphate, which causes them to be secreted outside the cell. As a result, lysosomes lack acid hydrolases and cannot break down complex macromolecules, leading to their accumulation.
I-cell disease can manifest at birth with coarse features, corneal clouding, organomegaly, hypotonia, and gingival hyperplasia. Failure to thrive, kyphoscoliosis, lumbar gibbus, and restricted joint movement are often present. There may also be hip dislocation, fractures, hernias, or bilateral talipes equinovarus, along with severe psychomotor retardation. Death occurs due to cardiorespiratory complications.
I-cell disease is diagnosed by testing the blood or urine for high levels of mucolipids, elevated plasma lysosomal enzyme concentration, decreased concentration of lysosomal enzymes in cultured fibroblasts, presence of inclusion bodies in peripheral blood lymphocytes, and low levels of UDP-N-acetylglucosamine-1-phosphotransferase enzyme activity in white blood cells. Differential is from Hurler syndrome.
Hurler and Hunter syndromes: They are mucopolysaccharidoses (MPS), a type of lysosomal storage disorder characterized by the deposition of mucopolysaccharides and glycosaminoglycans in tissues.
Zellweger syndrome and Refsum disease: Proteins destined to reach the peroxisomes are tagged with C-terminal peptides that function as a peroxisome targeting signal. In Zellweger syndrome and Refsum disease, this process is improper.
In Zellweger syndrome, very long chain fatty acids accumulate in the peroxisomes, and there is disruption of myelin synthesis. This causes hepatomegaly, mental retardation, seizures, hypotonia, retinal degeneration, etc.
Refsum disease is a less severe form with accumulation of phytanic acid, anosmia, vision loss, retinitis pigmentosa, scaly skin, and arrhythmias.
Disorders of galactose metabolism
In both disorders, a reducing substance (galactose) will be present in urine. If infants with classic galactosemia are not treated promptly with a low-galactose diet, life-threatening complications can appear within a few days after birth. Breast milk, proprietary infant formulas containing lactose, cow’s milk, dairy products, and casein- or whey-containing foods, as well as medications with lactose and galactose, are avoided. Women with classic galactosemia should maintain a lactose-restricted diet during pregnancy.
*Common reducing substances that may be present in urine are glucose, fructose, lactose and galactose.
Therapy for fructose intolerance is a fructose-free diet. Early fructose restriction can prevent damage to the liver and kidneys.
Medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency: It is a disorder of medium-chain fatty acid β-oxidation. It presents in infancy with hypoketotic hypoglycemia, vomiting, lethargy, hepatomegaly, seizures, and coma triggered by illness or fasting. Management is by frequent feedings to prevent hypoglycemia, avoidance of fasting, and restricting medium-chain triglycerides such as coconut oil, MCT oil, and some infant formulas.
Lesch-Nyhan syndrome: It is an X-linked recessive disorder caused by deficiency of hypoxanthine-guanine phosphoribosyltransferase (HGPRT). It is a hereditary disorder of purine metabolism associated with increased uric acid production. It presents with compulsive self-mutilation (including biting and head banging), gout, kidney stones, bladder stones, moderate cognitive disability, and involuntary muscle movements. Patients typically cannot walk, require assistance sitting, and generally use a wheelchair. Death occurs in early adulthood from renal failure.
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