INBORN ERRORS OF METABOLISM

INBORN ERRORS OF CARBOHYDRATE METABOLISM

GALACTOSAEMIA caused by loss-of-function mutations in the GALT gene which encodes galactose-1-phosphate uridyl transferase. inherited as an autosomal recessive disorder Vomiting or diarrhoea usually begins within a few days of ingestion of milk Failure to thrive is the most common clinical presentation. hepatomegaly, cataracts and mental retardation fulminant infection with Escherichia coli is a frequent complication Treatment involves life-long avoidance of galactose- and lactose-containing foods

GLYCOGEN STORAGE DISEASES Result from an inherited defect in one of the many enzymes responsible for the formation or

breakdown of glycogen There are several major types of GSD Most forms of GSD are inherited as autosomal recessive disorders Different types of GSD present at different ages

DISORDERS OF LIPID METABOLISM

lysosomal storage diseases are disorders caused by loss-offunction mutations in various lysosomal enzymes

inability to break down complex glycolipids diverse clinical manifestations, typically including mental retardation

Fabry disease:C/F:Variable age of onset.Neurological (pain in extremities)Dermatological (hypohidrosis,angiokeratomas)Cerebrovascular (renal, cardiac, central nervous system) Enzyme deficiency: α-galactosidase A

Gaucher disease: Splenic and liver enlargement, with variable severity of disease Some types also have neurological involvementEnzyme deficiency:GlucocerebrosidaseMucopolysaccharidosis (MPS) Hurler’s,Hunter’s,Sanfilippo’s and

Morquio’s syndromes):Can cause mental retardation, skeletal and joint abnormalities,abnormal

facies, obstructive respiratory diseases and recurrent respiratory infections

Niemann–Pick disease:progressive neurological disorder,accompanied by organomegalyEnzyme deficiency:Acid sphingomyelinaseGM2-gangliosidosis ( Tay–Sachs and Sandhoff diseases):Severe progressive neurological disorder, Sandhoff also

characterised by organomegalyEnzyme deficiency:Hexosaminidase A, B

DISORDERS OF AMINO ACID METABOLISM

PHENYLKETONURIA inherited as an autosomal recessive disordercaused by loss-of-function mutations in the PAH genephenylalanine accumulates at high levels in the neonate’s blood

causing mental retardationDiagnosis by routine neonatal screeningTreatment involves a life-long adherence to a low-phenylalanine

diet

HOMOCYSTINURIA autosomal recessive loss-of-function mutations in the CBS gene which encodes cystathionine beta–synthase causes accumulation of homocysteine and methionine in the blood Clinical manifestations: eyes :ectopia lentis central nervous system: mental retardation, delayed developmental milestones,

seizures, psychiatric disturbances skeleton :resembling Marfan’s syndrome, generalised osteoporosis vascular system:thrombotic lesions of arteries and veins skin:hypopigmentation.

Diagnosis: through newborn screening programmesTreatment:a methionine restricted,cystine-supplemented diet, as well as large

doses of pyridoxine