This document summarizes cases of inborn errors of metabolism (IEM) diagnosed in the Jeddah region from 2010-2013. It presents two relatively rare case studies in more detail: a 2-year-old with Aminoacylase 1 deficiency who is developing normally, and a 5-year-old with 3-Methylcrotonyl-CoA carboxylase (3MCC) deficiency who is managing well with a leucine-free diet and carnitine. Overall, the document provides statistics on various IEM cases diagnosed, discusses the classification and presentation of small-molecule disorders and lysosomal storage disorders, and reviews the diagnosis and management of Aminoacylase 1 deficiency and

1. Spectrum of IEM disease in Jeddah
region

2. POINTS IN THE PRESENTATION
• 1-list of metabolic cases diagnosed or referred
to the MCH from 2010-2013
• 2-their follow up and condition in the present
time
• 3-presentation of rare metabolic cases
• 4-discussion of 2 relatively rare disorders of
diagnosed cases

3. Inborn errors of metabolism (IEM) can be
classified according to the size of
accumulated or deficient metabolites into
small-molecule disorders such as
aminoacidemia, organic acidopathies, urea
cycle defect, galactosemia, fatty acid
oxidation disorders, and other disorders
such as glycogen and lysosomal storage
and organelle diseases.

4. small-molecule disorders
DISEASE CATOGRIES
NUMBER OF CASES DIAGNOSED
Number of deaths
PPA
7
4
IVA
3
-
B KETOTHYOLASE
DEFECIENCY
6
2
MMA
4
PKU
2
-
TYROSENEMIA
1
-
MCAD
2
-

5. DISEASE CATOGRIES
NUMBER OF CASES DIAGNOSED
Number of deathes
GAU1
5
-
VLCAD
2
-
CPT1
1
-
NKH
2
UCD
3
2
HOMOCYSTINURIA
1
-
MSUD
6
-

6. DISEASE CATOGRIES
NUMBER OF CASES DIAGNOSED
Number of deaths
HMG COLYASE
1
-
3MCC DEFECEINCY
2
-
AMINOAYCLASE 1
DEFECIENCY
1
-

7. STOREGE DISORDERS
DISEASE CATOGRIES
NUMBER OF CASES
DIAGNOSED
Number of deaths
MPS1
3
-
MPSVI
4
-
POMPE
2
1
GOUCHER DISEASE
2
-

8. CASESE 1
•
•
•
•
2 years old
Product of ClS
Neonatal jaundice
Elevated glturyl carnatine in
neonatal screening
• Seen at my clinic at the age of 2 m
• completely healthy with normal
examination of all body systems
• Now at 2y of age , normal
development, no attacks of
seizure, normal muscle tone and
reflexes,

9. • Tandem ms done was normal
• Urine GC-MS showed –(2M)
Elevated N-acetylated amino acids
N-acetylmethyonine
N-acetylglutamic
N-acetylglycine
Test repeated after 5 months—same result
Result suggestive of Aminoacylase 1 deficiency

10. Aminoacylase 1 deficiency
• Aminoacylase (ACY1) is a zinc binding enzyme
which hydrolyzes N-acetyl amino acids into
the free amino acid and acetic acid
• Of the N-actyl amino hydrolyzing
enzymes, aminoacylase 1 is the most common
• The ACY1 gene is located on the short arm of
chromosome 3 (3p21.2).

11. • function as a tumor suppressor gene in small
cell lung cancer and in renal carcinoma,
• may also play a role in monitoring responses
to oxidative stress and in regulation of cellular
red ox status.

12. The clinical picture
• heterogeneous
• motor delay, seizure, moderate to severe
mental retardation, absent speech, growth
delay, muscular hypotonia and autism ,autistic
feature.

13. • It remains uncertain whether ACY1 deficiency has
pathogenic significance with pleiotropic clinical
expression or is simply biochemical variant.
• The organic acids analysis that led to the
detection of ACY1 deficiency is part of selective
screening for inborn errors of metabolism, which is not
performed routinely in healthy
children but only in individuals in whom a metabolic
disease is considered, resulting in a strong bias
• However its expression in the central nervous system in
human, suggested a role of the enzyme in the amino
acid metabolism of these organ

14. • Van Coster et al. (2005) reported an infant with
aminoacylase-1 deficiency presented neonatally with
an acute encephalopathy with onset on the third day of
life. Clinical features included seizures, apnea,
vomiting, hypotonia, and sensorineural hearing loss.
• Urinalysis detected several N-acetylated amino acids.
• MRI showed cerebral atrophy. At age 9 months, he had
reached normal developmental milestones and there
were no abnormal clinical neurologic signs.

15. • Sass et al. (2006) presented 4 children with a genetic
deficiency of ACY1 identified through organic acid
analyses.
• The clinical phenotypes of the patients were
heterogeneous:
• 1 subject-- nonspecific psychomotor delay
• Second subject --psychomotor delay with atrophy of
the vermis and syringomyelia
• in a third ---marked muscular hypotonia,
• the fourth subject -- follow-up for early treated
biotinidase deficiency with normal clinical findings

16. • Sass et al. (2007) reported 3 additional patients with ACY1
deficiency detected through newborn screening
• Two patients were born of consanguineous parents of Asian and
Romani origin, respectively. The Asian child presented with febrile
seizures at 11 months of age, followed 3 months later by more
seizures associated with a viral illness. She showed delayed speech
and language development at age 4 years.
• The Romani child had onset of multifocal, drug-resistant epilepsy
with atonic, tonic, and absence seizures at age 1 year. He was
hyperactive with moderate mental retardation.
• The third patient, of English origin, presented at 11 months with a
prolonged generalized seizure and transient hemiplegia associated
with illness. She showed complete recovery and normal
development at age 19 months.

17. Case 2
• Aseel 5years old female
• SVD, APGAR 9/10/, BW=2.8KG
• Newborn screening=increased of
C5-hydroxy acylcarnitine in blood
•
increased 3 hydroxi isovalaric and
3 methylCartonyl glycin in Urine
Developed one attack of
decompansation,managed at her local
hospital
 Referred to my clinic at the age of one
Month,

18. • Metabolic tests done Confirmed the diagnosis
3-Methylcrotonyl-CoA carboxylase deficiency
(3MCC deficiency )
• Managed
• Diet- leucine free formula- carnatine
• Now she is 4 years , with normal development

19. Case 2
• Abdullah 2 years old male
• Diagnosed by neonatal screening
As 3 MCC defeciency
• Started on leucine free formula
• L-carnatine
• Did well , but at the age of
6 months mother started to give
him regular food , because he was
refusing the formula
•
Patient now at the age of 2 years with
normal development, no attacks of
decompansation

20. 3-Methylcrotonyl-CoA carboxylase
deficiency (3MCC deficiency
• -MethylCrotonyl-CoA Carboxylase (3-MCC)
Deficiency has been recognized since 1984. It
is a defect in the degradation of the amino
acid leucine

21. CLINICAL PRESENTATION
• Varies --severe –mild
• Onset—usually during first year ,later onset, even asymptomatic adult
• 1-catabolic
• vomiting, lethargy, apnea, hypotonia, seizures, profound
hypoglycemia, metabolic acidosis, hyperammonemia,.
2-failure to thrive
• beginning in the neonatal period or developmental delay
• Asymptomatic
• women with 3-MCC deficiency may pass along the 3-MCC metabolite
transplacentally to their infants, who are then found to have elevated 3MCC by newborn screening with tandem mass spectrometry, but who
themselves do not have the disease

22. diagnosis
• tandem mass spectrometry reveals an elevation of C5hydroxy acylcarnitine
• organic acid analysis finds elevation of 3-hydroxyisovaleric
acid and usually 3-methylcrotonylglycin
• enzyme activity should be assayed in fibroblasts or
leukocyte
• 3-MCC activity can also be measured in chorionic villus
specimens
• Mothers of all infants found to have elevated 3-MCC with
newborn screening should be tested with a blood
acylcarnitine profile to determine whether they have 3MCC deficiency rather than their infant.

23. Hope for future