Glutaric aciduria type 2 is an inherited disorder caused by a deficiency in electron transfer flavoprotein or electron transfer flavoprotein dehydrogenase, which help break down proteins and fats for energy. This leads to a buildup of partially broken down nutrients that damage cells, causing metabolic crises in infancy or early childhood with acidosis, low blood sugar, and other symptoms. In severe cases, physical abnormalities may also be present at birth. The condition is inherited in an autosomal recessive pattern and treatment involves high doses of riboflavin, carnitine supplements, and counseling.

1. GLUTARICACIDURIA TYPE 2
Soumya Ranjan Parida
Basic B.Sc. Nursing 4th
year
Sum Nursing College

2. INTRODUCTION
 Glutaric acidemia type II is an inherited disorder
that interferes with the body's ability to break down
proteins and fats to produce energy.
 Incompletely processed proteins and fats can build
up in the body and cause the blood and tissues to
become too acidic (metabolic acidosis).
 Glutaric acidemia type II usually appears in infancy
or early childhood as a sudden episode called a
metabolic crisis, in which acidosis and low blood
sugar (hypoglycemia) cause weakness, behavior
changes such as poor feeding and decreased
activity, and vomiting.
 These metabolic crises, which can be life-
threatening, may be triggered by common
childhood illnesses or other stresses.

3.  In the most severe cases of glutaric acidemia type
II, affected individuals may also be born with
physical abnormalities.
 These may include brain malformations, an
enlarged liver (hepatomegaly),
 a weakened and enlarged heart (dilated
cardiomyopathy),
 fluid-filled cysts and other malformations of the
kidneys,
 unusual facial features,
 and genital abnormalities.

4.  Glutaric acidemia type II may also cause a
characteristic odor resembling that of sweaty feet.
 Some affected individuals have less severe
symptoms that begin later in childhood or in
adulthood.
 In the mildest forms of glutaric acidemia type II,
muscle weakness developing in adulthood may be
the first sign of the disorder.

5.  Mutations in any of three genes, ETFA, ETFB, and
ETFDH, can result in glutaric acidemia type II.
 The ETFA and ETFB genes provide instructions for
producing two protein segments, or subunits, that
come together to make an enzyme called electron
transfer flavoprotein.
 The ETFDH gene provides instructions for making
another enzyme called electron transfer flavoprotein
dehydrogenase.
 Glutaric acidemia type II is caused by a deficiency
in either of these two enzymes.

6.  Electron transfer flavoprotein and electron
transfer flavoprotein dehydrogenase are
normally active in the mitochondria, which
are the energy-producing centers of cells.
 These enzymes help break down proteins
and fats to provide energy for the body.
 When one of the enzymes is defective or
missing, partially broken down nutrients
accumulate in the cells and damage them,
causing the signs and symptoms of glutaric
acidemia type II.

7.  People with mutations that result in a
complete loss of either enzyme
produced from the ETFA, ETFB or
ETFDH genes are likely to experience
the most severe symptoms of glutaric
acidemia type II. Mutations that allow
the enzyme to retain some activity
may result in milder forms of the
disorder.

8.  This condition is inherited in an
autosomal recessive pattern, which
means both copies of the gene in each
cell have mutations.
 The parents of an individual with an
autosomal recessive condition each
carry one copy of the mutated gene,
but they typically do not show signs
and symptoms of the condition

9.  Typical clinical features of the disorder are
respiratory distress, muscular hypotonia, sweaty
feet odor, hepatomegaly, and death often in the
neonatal period.
 Of the 12 previously reported cases reviewed by
Niederwieser et al. (1983), 7 died in the first 5 days
of life and only 2 patients survived to ages 5 and 19
years.
 Niederwieser et al. (1983) reported the case of the
son of consanguineous Jewish parents who died at
age 7 months. In a note added in proof, they
described the prenatal diagnosis of an affected
female of the same parentage, indicating autosomal
recessive inheritance.

10.  Patients with severe deficiency of the ETF
dehydrogenase type have distinctive congenital
malformations, whereas those with ETF deficiency
do not; the severity of the metabolic block, rather
than its location, and the resulting profound acidosis
in utero may disturb normal morphogenesis.
 Colevas et al. (1988) described the pathologic
findings in 2 cases. The pattern of lesions, in
particular the striking localization of renal dysplasia
to the medulla, suggested that the malformations
may be the consequence of an accumulation of
toxic metabolites that is not corrected by placental
transfer.


11.  Other malformations included cerebral
pachygyria, pulmonary hypoplasia, and
facial dysmorphism.
 Lipid accumulation was demonstrated in
the liver, heart, and renal tubular epithelium,
all tissues that use fatty acids as a primary
source of energy.

12.  Wilson et al (1989)found reports of malformations in
8 of 16 cases.
 The anomalies included macrocephaly, large
anterior fontanel, high forehead, flat nasal bridge,
telecanthus, and malformed ears.
 Abnormalities such as hypotonia, cerebral gliosis,
heterotopias, hepatomegaly, hepatic periportal
necrosis, polycystic kidneys, and genital defects
were considered reminiscent of the anomalies in
Zellweger syndrome, but elevations of glutaric,
ethylmalonic, adipic, and isovaleric acids were
considered distinctive for glutaric aciduria type II.

13.  Wilson et al. (1989) described a unique
ultrastructural change in the glomerular
basement membrane which they suggested
may represent an early stage in renal cyst
formation and provide a diagnostic criterion
for glutaric aciduria II when enzyme studies
are unavailable.

15.  The heterogeneous clinical features of patients with
MADD fall into 3 classes (Frerman and Goodman,
2001):
 a neonatal-onset form with congenital anomalies
(type I),
 a neonatal-onset form without congenital
anomalies (type II), and
a late-onset form (type III).
The neonatal-onset forms are usually fatal and are
characterized by severe nonketotic hypoglycemia,
metabolic acidosis, multisystem involvement, and
excretion of large amounts of fatty acid- and amino
acid-derived metabolites.

16. Symptoms and age at presentation of late-onset MADD
are highly variable and characterized by recurrent
episodes of lethargy, vomiting, hypoglycemia,
metabolic acidosis, and hepatomegaly often
preceded by metabolic stress.
Muscle involvement in the form of pain, weakness,
and lipid storage myopathy also occurs.
The organic aciduria in patients with the late-onset
form of MADD is often intermittent and only evident
during periods of illness or catabolic stress

17. TREATMENT
 High doses of RIBOFLAVIN –
100mg/day
 Syp carnitor- 100-150mg/day.
 Councelling of the parents.
 Prenatal diagnosis during next
pregnancy.

18. THANK YOU.