Autosomal Recessive Disorders Flashcards
What is the mnemonic of Autosomal Recessive disorder?
WHAT CAN FUSSY GAME DO
What are the Autosomal Recessive disorders?
W = Wilson’s disease
H = Haemochromatosis
Hurler syndrome
Hallervorden-Spatz disease
A = Ataxia Telangiectasia
T = Thalassemia (Beta)
Tay-Sach’s disease
C = Cystic fibrosis
Congenital Adrenal Hyperplasia (CAH)
Crigler Najjar syndrome
A = Abetalipoproteinaemia
Albinism
Autoimmune polyendocrinopathy syndrome (APS) type 1
N = Niemann-Pick disease
F = Freinreich’s ataxia
Familial mediterranean fever
Fanconi’s anaemia
U = (all -Uria) Phenylketonuria
Alkaptonuria
Cystinuria
Homocystinuria
Maple syrup urine disease
S = Storage disorders (Lysosomal, Glycogen, Lipid)
Syndrome Bartter’s (Bartter’s syndrome)
Syndrome Rotor (Rotor syndrome)
Syndrome Lawrens (Lawrens Moon Biedl syndrome)
S = Sickle cell anaemia
Y = MucopolYsaccaridosis (All, like Hurler’s; except Hunter)
G = Galactosemia
Gaucher’s disease
Gunther disease
Gilbert syndrome
Giltelman’s syndrome
G6PD deficiency (Von Gierke’s disease)
A = Adrenal hyperplasia (Congenital, CAH)
M = Muscular: atrophies, limb girdle muscular dystrophy
E = Emphysema (Alpha 1 Antitrypsin Deficiency)
Elasticum, pseudoxanthoma (Pseudoxanthoma elasticum) (few are AD)
D = Dubin Johnson syndrome
Deafness
O = Oculocutaneous Albinism
Autosomal Recessive disorders are almost always which type?
Structural/Metabolic
Metabolic
Name 4 metabolic disorders which are X-linked recessive
Hunter’s disease (= Mucopolysaccaridosis or MPS type 2)
G6PD deficiency
Adenoleukodystrophy (Childhood form)
Ornithine transcarbamoylase deficiency
Name 6 metabolic disorders which are autosomal dominant
Hyperlipidaemia type II (a,b)
Familial hypercholesterolemia (=hyperlipidaemia IIa)
Hypokalaemic periodic paralysis
Hyperthermia (Malignant)
Acute intermittent porphyria (AIP)
Porphyria cutanea tarda (PCT)
Variegate porphyria
Hurler’s disease comes into which category of disease?
Mucopolysaccharidoses
What is the inheritence pattern of mucopolysaccharidoses?
All mucopolysaccharidoses : Autosomal recessive
Hurler’s disease: Autosomal recessive
Hunter’s disease: X-linked recessive
Who are affected by autosomal recessive disorders?
heterozygotes/homozygotes/both?
Only homozygotes are affected and manifest the disease
Who are affected by autosomal recessive conditions?
Male or female?
Both
What is the carrier status for autosomal recessive disorders?
All heterozygous are carrier
Do autosomal recessive disorders manifest in every generation?
NO
Autosomal recessive do NOT manifest in every generation; may skip a generation
What are the possible combinations of genotype in parents/couple in recessive conditions?
Heterozygote carrier + normal
Heterozygote carrier + Heterozygote carrier
Heterozygote carrier + Homozygote (affected)
Homozygote (affected) + Homozygote (affected)
Homozygote (affected) + normal
If one parent is heterozygote carrier + another normal, what are the chances among children?
(can use pen & paper)
Each child has 0% chance of being affected (homozygote)
Each child has 50% chance of being a carrier (heterozygote)
Each child has 50% chance of being a normal
If both parents are heterozygote carriers, what are the chances among children?
(can use pen & paper)
Each child has 25% chance of being affected (homozygote)
Each child has 50% chance of being carrier (heterozygote)
Each child has 25% chance of being normal (not carrier/affected) child (i.e. genotypical child)
If one parent is heterozygote carrier + another homozygote (affected), what are the chances among children?
(can use pen & paper)
Each child has 50% chance of being affected (homozygote)
Each child has 50% chance of being carrier (heterozygote)
If both parents are homozygotes (affected), what are the chances among children?
(can use pen & paper)
Each child has 100% chance of being affected (homozygote)
If one parent is homozygote (affected) + another normal, what are the chances among children?
(can use pen & paper)
Each child has 0% chance of being affected (homozygote)
Each child has 0% chance of being normal
- *All the children** will be carrier (heterozygote) =
- *100% chance** of having a carrier (heterozygote) child
How many mutated copies/alleles of the autosomal gene is needed to manifest the disease?
2 (two)
Autosomal recessive conditions are almost always metabolic,
But, as an exception, which are structural?
AR structural conditions:
Ataxia telangiectasia (inherited ataxia)
Friedrich’s ataxia (inherited ataxia)
Oculocutaneous albinism
What is the inheritence of lipid storage disorders?
Autosomal recessive
What are the lipid storage diseases?
Tay-Sach’s disease
Gaucher disease
Niemann-Pick disease
What is the underlying pathology of Gaucher disease?
Deficiency of glucocerebrocidase enzyme >>>>> excess glucocerebrocide accumulates in cells, organs
Increased acid phosphatase activity
What are the common features of Gaucher’s disease?
Anaemia >> fatigue
Low platelets >> bruising
Hepatomegaly
Splenomegaly
What is the underlying pathology in Tay-Sach’s disease?
Excess ganglioside accumulation in brain >>>>> premature nerve cell death
In which race, Tay-Sach’s is more common?
Askenazi Jews population
What are the usual manifestations of Tay-Sach’s?
At 7months of age >>>>> Low mental & physical abilities
At around 4years >>>>> Death
Inheritance of G6PD deficiency
G6PD deficiency (favism) >>> X-linked recessive
G6PD deficiency (Von Gierke’s disease) >>> Autosomal recessive
Only G6PD deficiency (if asked) >>> Consider X-linked recessive (more common)
What special inheritance may be seen in hereditary haemochromatosis?
Pseudodominant
What is pseudodominant inheritance in hereditary haemochromatosis?
As carrier frequency is high (>1 per 10) >>> often partner of an affected person is conincidentally a carrier >>> 50% of his or her offspring will have a genotype of clinically affected haemochromatosis = so, psueo-dominant (/vertical dominant transmission is observed)
In haemochromatosis, if both alleles are mutated, will all become symptomatic?
NO. Only a few of them will be symptomatic
What is the penetrance of haemochromatosis in different sex?
Penetrance is higher in males than females
What is Hallervorden Spatz disease?
It is rare neurodegenerative condition due to increased iron accumulation
Hallervorden spatz disease: genetic defect
Chromosome 20
Gene PANK2
Encodes: pantothenate kinase 2
Hallervorden Spatz disease: features
Childhood or Adolescence
- Pyramidal/extrapyramidal signs
- Dementia
- Optic atrophy
MRI: Eye of the tiger signs (due to increased Fe in basal ganglia)
What is Pseudoxanthoma elasticum?
Abnormal elastic fibres
Pseudoxanthoma elasticum: Features
- Retinal angioid streaks
- Plucked chiken skin appearance >> small yellow papules on the neck, antecubital fossa and axilla
- Cardiac: mitral valve prolapse (MVP)
- GI haemorrhages
(Mitral valve prolapse is also seen in Marfan syndrome, Fragile X syndrome)
What is Galactosaemia?
Intracellular accumulation of galactose-1 phosphate
Galactosaemia: Enzyme deficiency
Deficiency of galactose-1-phosphate uridyl transferase
Galactosaemia: Features
- Jaundice
- Cataracts
- Failure to thrive
- Hypoglycaemia (after exposure to galactose)
- Hepatomegaly
- Fanconi syndrome
Galactosaemia: diagnosis
Reducing substances in urine
Galactosaemia: management
Galactose free diet
