CELL BIOLOGY AND GENETICS

DIGITAL ASSIGNMENT I

Harittha Parameswaran|17BBT0263
 ACHONDROGENESIS
Achondrogenesis is the collective name for a group of
disorders which are the most severe form of malformation
of bones and cartilage or chondrodysplasia. It is a
congenital disorder, characterized by infants born with short
limbs, a tiny body etc., among other skeletal deformations
which usually results in stillbirth or death shortly afterward.
The disease has 3 different manifestations, type 1A, type 1B
and type 2, each type distinguished by unique signs and
symptoms.
The cell organelle affected is the Golgi Apparatus. This
organelle’s main function is to modify, package and sort the
immense variety of macromolecules synthesized by the cell.
TYPE 1A or Houston-Harris type:
▪ Symptoms:
o Facial deformities (protruding eyes and tongue),
short limbs, thin cranial and spinal bone formation.
o Premature development of thorax causes lung
dysfunction and death.
▪ Inheritance:
o Autosomal recessive
▪ Cause:
o Mutations in TRIP11, which codes for the protein
GMAP-210, associated with Golgi Apparatus.
o GMAP-210 plays a key role in the development of
Chondrocytes, which are responsible for proper
bone and cartilage formation.

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TYPE 1B or Parenti-Fraccaro type:
▪ Symptoms:
o Narrow chest, rounded abdomen, clubbed feet,
hernia,
▪ Inheritance:
o Autosomal recessive
▪ Causes:
o Mutations in SLC26A2 gene
o SLC26A2 codes for a transmembrane
glycoprotein of the same name, involved in bone
and cartilage formation.
TYPE 2 or Fraccaro type:
▪ Symptoms:
o Cleft palate, enlarged abdomen, a condition called
hydrops fetalis, where there is excess fluid
buildup in the body prior to birth.
▪ Inheritance:
o Autosomal dominant
▪ Causes:
o Mutations in the gene COL2A1
o The gene codes for a type of collagen present in
the cartilage and the vitreous humor of the eye.
o Mutations cause interference in the proper
assembly of the protein, which prevents proper
bone and cartilage development.

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Treatment:
Treatment as such is unavailable for the disease, as most
affected infants are either stillborn or die shortly afterward,
owing to complications. Since types 1A and 1B are inherited in
an autosomal recessive manner, the chances of the child
inheriting it are only when both parents are carriers, and in
cases which they are, the child inheriting it is given a 25%
possibility. Type 2 being inherited in an autosomal dominant
manner, couples are advised to usually go for genetic
counseling.

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 POMPE’S DISEASE
Pompe’s disease is a genetic disorder, caused due to the
accumulation of glycogen in the body which leads to
malfunctioning of many organs in the body. It has 3 different
manifestations- classic infantile onset, non-classic infantile
onset, and late onset.
The affected organelle is the lysosome. The disease is caused
due to the accumulation of glycogen in the lysosomes, due to
the deficiency of an enzyme responsible for glycogen
breakdown.
▪ Inheritance:
• Autosomal recessive disorder.
▪ Symptoms:
• Classic Infantile onset:
o Most severe form, usually symptoms show up
after 3 months following birth.
o Rapidly progressive muscle weakness or
floppiness of muscles
o Hypotonia reduces muscle toning
o Hypertrophic Cardiomyopathy – thickening
of left chambers of the heart and the septum,
in an abnormal way.
o Ultimately leads to Cardiorespiratory
failure within 2 years of life.
• Non-Classic Infantile onset:
o Sleep apnea – shallow or pauses in breathing
while asleep
o Respiratory insufficiency

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 o Intolerance to exercise
• Late Onset:
o Doesn’t show up till late childhood
o Progressive muscle weakness
o Respiratory difficulties
▪ Cause:
• Mutations in the gene GAA, present on
chromosome 17 which codes for the lysosomal
hydrolytic enzyme, Acid Alpha-Glucosidase.
• The enzyme is responsible for breaking down
glycogen to glucose
• The mutated gene causes a deficiency of the
enzyme and hence leads to accumulation of
glycogen.
▪ Treatment:
• Diagnosis is mainly done by a detailed clinical
analysis of the patient’s family pedigree, and a
variety of specific tests and assays.
• Enzyme Replacement Therapy:
o The recombinant form of the enzyme acid
alpha-glucosidase is administered
intravenously.
• Supportive Therapy
o Physiotherapy for strengthening muscles
o Respiratory support therapies.
• Gene Therapy
o Investigations are being conducted, involving
stem cell therapies and other advanced
therapies.

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The first image shows a muscle biopsy, with large vacuoles, a
symptom of Pompe’s disease.

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 ZELLWEGER’S SYNDROME
Zellweger’s syndrome belongs to a family of disorders called
Zellweger spectrum of Disorders. The main characteristic of
this syndrome is the absence of functional peroxisomes in the
cells of affected individuals. It is also known as a
cerebrohepatorenal syndrome.
▪ Inheritance:
• Autosomal Recessive
▪ Types and Symptoms:
• Appear around the infantile period.
• Low muscle toning
• Hearing and vision loss
• Seizures
• Children also develop other lethal problems in
other organs of the body such as the heart, liver,
kidneys etc.
▪ Cause:
• Mutations in any of the 12 different genes
responsible for the creation and proper functioning
of peroxisomes, called PEX genes.
• Peroxisomes are involved in the metabolism of fatty
acids
• The absence of these organelles leads to
accumulation of very long chain fatty acids and
branched fatty acid chains in the cell, which
interferes with the proper functioning of many
other major organs of the body.

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 • A breakdown of myelin also occurs, in the spinal
cord and brain (white matter). Myelin enables the
quick transmission of nerve impulses.
Demyelination causes loss of white matter.
▪ Diagnosis:
• The condition is usually diagnosed at birth by
identifying certain characteristic features and
symptoms
• Blood and urine tests are also used.

▪ Treatment:
• There is no effective treatment as such available for
the disease, though researchers are going on
• Infants with feeding problems may be supported
via a feeding tube but, they do not survive past 6
months of life
• Affected patients often succumb to respiratory
disorder and pneumonia.

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