Gene imprinting

Examples:
Prader-Willi and Angelmansyndromes
and Beckwith-Wiedemann and
Russell-Silver syndromes

Hyperammonia

Sample should be sent in ice arterial blood preffered

Genetic testing registry

,

Pompe synd

Hypotonia with cardiomyopathy

Absent stomach bubbles

Causes: esophageal atresia, TOF, micrognathia causing obstruction, neuromuscular disorders causing reduced peristalsis
,

Inborn Error Of Metabolism

Factors wich precipitate acute illness in IEM
1. Diet:
Cane sugar : hereditary fructose deficiency
Milk: Galactosemia
Protein: Urea Cycle disorders, aminoacidopathy
Carbohydrates: pyruvate dehydrogenase and respiratory chain disorders

2. Infection, fasting and fever: Fatty acid Oxidation defects, few amino acid defects and organic aciduria.

3.Anaesthesia CD56e: in Homocystinuria

4. Drugs: porphyria and G6 Pd deficiency

Porphyria: group of disorder related to haem synthesis, involves dysfunction of enzyme necessary for haen synthesis

Two types, erythrocyte type(85%of haen synthesis occur in erythrocyte) and hepatic type(remaining 15%)

. 

If blood gases show an anion gap and metabolic acidosis , with hyperammonia...think of organic acid uria

Tyrosinaemia: succinylacetone to be done, alkaline phosphatase is high. Hepatosplenomegaly present

+Low iq , hyperactivity and autistic behaviour...D/d is phenylketonuria

+In fanconi anaemia, along with renal involvement check for signs of vitamin D resistant tickets

+ Oligosaccharidosis have similar phenotype as of mps that is coarse face, ham, bone dysplasia etc 

For screening , urine oligosaccharidosis are done,( this test has been done in few center only)

 Oligosacch..  are ab sent in few oligosaccharidosis like  

beta-mannosidosis, mucolipidosis II, and mucolipidosis III, 

May be detected in, Pompe disease (a glycogen storage disease), as well as Gaucher and Sandhoff diseases (sphingolipidoses). 

Fatty Acid Oxidation defect:

long-chain fatty acids (C16–C20) : mimics mitochondrial defects, presents as severe neonatal lactic acidosis, cardiomyopathy and hepatopathy.

CDG

Cerebellar atrophy is hallmark of CDG

+Child looking like MPS, but with normal urine screen

Disease   - enzyme def

GM 1 gangliosidisis - beta d galactosidase

+ Gaucher dis - GBA gene, 4 common mutation

L444P

N370S

84GG

IVS2+1

+ Odour --disease

Animal like.....PKU

Maple syrup.....MSUD

Cabbage like.....tyrocinemia 1, methionine malabsorption

Rotten fish..... Trimethylamine uria, dimethyl glycine uria

SKELETAL DYSPLASIA

ACHONDROPLASIA
S
Large C/f: disproportionate dwarfism: proximal limbs are shorter(Rhizomelic)
Short toe and fingers which is K/a Trident hand
Frontal bossing and large hand
Flat nasal bridge and midface hypoplasia
Spinal kypohosis or lordosis
Recurrent ear infection due to blockage of ETube
Varus/ valgus knee deformity

Genetics: AD, affected individual s are all heterozygous since homozygosity is lethal to foetus.
Mutation in fGFR 3 gene


PSEUDOACHONDROPLASIA:

features are similar to achondroplasia except macrocephaly and facial dysmorphism
form of spinoepiphyseal dysplasia
4 character: bowing of legs: genu valgum
                    laxity of all joints except elbow which has contracture
                    small irregular epiphysis, irregular broad metaphysis of long bones.
                 



SKELETAL DYSPLASIA WITH HEARING IMPAIRMENT:
1. diastrophic dysplasia
2. spondyloepiphyseal dysplasia congenita
3. morquio syndrome


+ Spondyloepiphyseal dysplasia seen in stickler syndrome