Metabolic Flashcards
What is Methylmalonicacidaemia?
- Autosomal recessive organic acidaemia
- Presents as a neonate
- High levels of methylmalonic acid and secondary hyperammonia
- Progressive encephalopathy
- Unable amino acids methionine, threonine, isoleucine and valine
- 60% cases from mutation in the MUT gene
- Encodes the protein methylmalonyl CoA mutase (converts methymalonyl CoA to succinyl CoA)
What severe vitamin deficiency can mimic MMA?
- Severe vitamin B12 deficiency
- need B12 to convert methymonyl CoA to succinyl CoA
- presents with methymonyl acidemia with exact sx and requiring same treatment
What types of metabolic disorders present with hepatosplenomegaly?
Storage disorders
What metabolic disorders present with massive hepatomegaly and a normal spleen?
Glycogen storage disease
Because glycogen is not stored in the spleen
What is GLUT1 deficiency?
Genetic disorder caused by SLC2A1 mutation.
GLUT1 is a glucose transporter present in all human tissues, particularly responsible for glucose transport across the blood brain barrier.
Diagnosis is low glucose in CSF
Common cause of seizures <4 years old with early onset absence seizures
The phenotypic spectrum also includes other forms of generalised epilepsies, developmental delay and paroxysmal exertional dyskinesias that usually emerge during childhood or adolescence
DIFFERENT from GLUT3 which does NOT cause low CSF gluc
Glutaric aciduria type 1
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Muccopolysaccharidoses
- MPS is a group of metabolic disorders caused by the absence or malfunctioning of LYSOSOMAL ENZYMES need to break down glycosaminoglycans. Therefore, the glycosaminoglycans accumulates in cells, blood, and tissues.
- This results in permanent, progressive cellular damage which affects physical appearance, physical abilities, organ and system functioning and usually development.
4 types with subtypes
some examples:
Hunter, Hurler, sanfillipo and morquio
Zellwegger syndrome
AKA cerebrohepatorenal syndrome
Peroxisome biogenesis disorder (most severe of PBD-ZSD spectrum)
Rare autosomal recessive (1 in 100,000)
Progressive degeneration of liver and kidneys
Fatal 6-12 months
Facies: High forehead, hypoplastic supraorbital ridges, epicanthal folds, midface hypoplasia, and a large fontanelle
Sx: Severe generalized hypotonia Profound GDD (impaired neuronal migration and development) Seizures, apnoea, poor feeding Hepatomegaly Renal cortical cysts Stippled calcifications of patella and greater trochanter Ocular abnormalities
Hepatic cells lack peroxisomes
Neonatal adrenoleukodystrophy
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Peroxisome biogenesis disorder (PBS-ZSD spectrum)
Refsum disease
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Peroxisome biogenesis disorder (PBS-ZSD spectrum)
Neonatal cholestasis - approach
Divide into Intrahepatic or extrahepatic
Intrahepatic
- Hepatic injury
- Metabolic disease
- -> inborn errors of metabolism (i.e zellwegers)
- -> Progressive familial intrahepatic cholestasis
- ->Disorders of membrane transport and secretion
- Viral
- Idiopathic neonatal hepatitis
- Bile duct injury
- Intrahepatic bile duct hypoplasia or paucity
–> disorders of embryogenesis
(most common is Alagille syndrome
Extrahepatic
- extrahepatic disease or obstruction
- Choledochal cyst
- Sepsis - Extrahepatic biliary atresia
Glycogen storage disease
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McArdle disease
-Glycogen storage disease type V and the most common type of glycogen storage disease.
- autosomal recessive disorder caused by mutations in the gene that encodes myophosphorylase, an enzyme that is essential for glycogenolysis.
- Exercise intolerance usually develops during childhood, along with pain, cramps, and fatigue in exercised muscle
Hurler syndrome
- This is caused by mutations of IUA gene encoding alpha L-iduronidase.
- It is severe, progressive with multiple organs/tissues involved, and it usually leads to death by 10 years
- Patients can appear normal at birth, may have inguinal hernias.
- It is diagnosed at 6-24 months with: hepatosplenomegaly; coarse facial features; large tongue; prominent forehead; joint stiffness; short stature.
Gaucher disease
- The most common lysosomal STORAGEdisease.
- It is a multisystemic lipidosis characterised by haematologic problems, organomegaly, skeletal involvement (bone pain, pathological fractures).
- It results from deficient activity of lysosomal hydrolase, acid B-glucosidase, causing accumulation of undegraded glycolipid substrates (especially glucosylceramide) in cells of the reticuloendothelial system.
- Progressive deposition results in: infiltation of bone marrow; hepatosplenomegaly; skeletal complications.
- Gaucher disease type 2 has the earliest onset, within the first 3 to 6 months of life and it is fatal; causing death before 2 years of age.
- Due to the shortened lifespan, babies with Type 2 will not survive long enough to develop the symptoms experienced by individuals with Type 1 and Type 3.
