Autosomal Recessive Disorders Flashcards

1
Q

What is the mnemonic of Autosomal Recessive disorder?

A

WHAT CAN FUSSY GAME DO

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2
Q

What are the Autosomal Recessive disorders?

A

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

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3
Q

Autosomal Recessive disorders are almost always which type?

Structural/Metabolic

A

Metabolic

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4
Q

Name 4 metabolic disorders which are X-linked recessive

A

Hunter’s disease (= Mucopolysaccaridosis or MPS type 2)

G6PD deficiency

Adenoleukodystrophy (Childhood form)

Ornithine transcarbamoylase deficiency

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5
Q

Name 6 metabolic disorders which are autosomal dominant

A

Hyperlipidaemia type II (a,b)

Familial hypercholesterolemia (=hyperlipidaemia IIa)

Hypokalaemic periodic paralysis

Hyperthermia (Malignant)

Acute intermittent porphyria (AIP)

Porphyria cutanea tarda (PCT)

Variegate porphyria

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6
Q

Hurler’s disease comes into which category of disease?

A

Mucopolysaccharidoses

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7
Q

What is the inheritence pattern of mucopolysaccharidoses?

A

All mucopolysaccharidoses : Autosomal recessive

Hurler’s disease: Autosomal recessive

Hunter’s disease: X-linked recessive

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8
Q

Who are affected by autosomal recessive disorders?

heterozygotes/homozygotes/both?

A

Only homozygotes are affected and manifest the disease

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9
Q

Who are affected by autosomal recessive conditions?

Male or female?

A

Both

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10
Q

What is the carrier status for autosomal recessive disorders?

A

All heterozygous are carrier

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11
Q

Do autosomal recessive disorders manifest in every generation?

A

NO

Autosomal recessive do NOT manifest in every generation; may skip a generation

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12
Q

What are the possible combinations of genotype in parents/couple in recessive conditions?

A

Heterozygote carrier + normal

Heterozygote carrier + Heterozygote carrier

Heterozygote carrier + Homozygote (affected)

Homozygote (affected) + Homozygote (affected)

Homozygote (affected) + normal

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13
Q

If one parent is heterozygote carrier + another normal, what are the chances among children?

(can use pen & paper)

A

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

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14
Q

If both parents are heterozygote carriers, what are the chances among children?

(can use pen & paper)

A

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)

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15
Q

If one parent is heterozygote carrier + another homozygote (affected), what are the chances among children?
(can use pen & paper)

A

Each child has 50% chance of being affected (homozygote)
Each child has 50% chance of being carrier (heterozygote)

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16
Q

If both parents are homozygotes (affected), what are the chances among children?
(can use pen & paper)

A

Each child has 100% chance of being affected (homozygote)

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17
Q

If one parent is homozygote (affected) + another normal, what are the chances among children?
(can use pen & paper)

A

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
18
Q

How many mutated copies/alleles of the autosomal gene is needed to manifest the disease?

19
Q

Autosomal recessive conditions are almost always metabolic,

But, as an exception, which are structural?

A

AR structural conditions:

Ataxia telangiectasia (inherited ataxia)

Friedrich’s ataxia (inherited ataxia)

Oculocutaneous albinism

20
Q

What is the inheritence of lipid storage disorders?

A

Autosomal recessive

21
Q

What are the lipid storage diseases?

A

Tay-Sach’s disease

Gaucher disease

Niemann-Pick disease

22
Q

What is the underlying pathology of Gaucher disease?

A

Deficiency of glucocerebrocidase enzyme >>>>> excess glucocerebrocide accumulates in cells, organs

Increased acid phosphatase activity

23
Q

What are the common features of Gaucher’s disease?

A

Anaemia >> fatigue

Low platelets >> bruising

Hepatomegaly

Splenomegaly

24
Q

What is the underlying pathology in Tay-Sach’s disease?

A

Excess ganglioside accumulation in brain >>>>> premature nerve cell death

25
**In which race, Tay-Sach's is more common?**
**Askenazi Jews population**
26
**What are the usual manifestations of Tay-Sach's?**
**At 7months** of age \>\>\>\>\> **Low mental & physical abilities** **At** around **4years** \>\>\>\>\> **Death**
27
**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)**
28
**What special inheritance may be seen in hereditary haemochromatosis?**
**Pseudodominant**
29
**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)**
30
**In haemochromatosis, if both alleles are mutated, will all become symptomatic?**
**NO. Only a few of them will be symptomatic**
31
**What is the penetrance of haemochromatosis in different sex?**
**Penetrance is higher in males than females**
32
**What is Hallervorden Spatz disease?**
**It is rare neurodegenerative condition due to increased iron accumulation**
33
**Hallervorden spatz disease: genetic defect**
**Chromosome 20** **Gene PANK2** **Encodes: pantothenate kinase 2**
34
**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)**
35
**What is Pseudoxanthoma elasticum?**
**Abnormal elastic fibres**
36
**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** ## Footnote **​**(Mitral valve prolapse is also seen in Marfan syndrome, Fragile X syndrome)
37
**What is Galactosaemia?**
**Intracellular accumulation of galactose-1 phosphate**
38
**Galactosaemia: Enzyme deficiency**
Deficiency of **galactose-1-phosphate uridyl transferase**
39
**Galactosaemia: Features**
* **Jaundice** * **Cataracts** * **Failure to thrive** * **Hypoglycaemia (after exposure to galactose)** * **Hepatomegaly** * **Fanconi syndrome**
40
**Galactosaemia: diagnosis**
**Reducing substances in urine**
41
**Galactosaemia: management**
**Galactose free diet**