Case history: 1

The following are the findings in a patient brought to the hospital in a coma state.

Fasting Plasma Glucose (GOD-POD basis) : 270mg%

Urine Benedict’s test : Positive

Urine Rothera’s test : Positive

Plasma pH : 7.20

1. Give probable diagnosis

2. What is the condition indicated by positive Rothera’s test and give the biochemical
mechanism for the complication ?
3. What is the normal pH? Give the biochemical mechanism resulting in altered pH in this
condition?
4. Give the reason for positive Benedict’s test in this condition?
5. Mention the principle of the GOD-POD method. Name the other methods (any two; one
enzymatic and one non-enzymatic)

1. The probable diagnosis for this patient is diabetic ketoacidosis (DKA). DKA is a serious
complication of diabetes that occurs when your body produces high levels of blood acids
called ketones.

2. The condition indicated by a positive Rothera's test is the presence of ketones in the
urine. The biochemical mechanism for this complication involves the breakdown of fatty
acids in the liver, leading to the production of ketone bodies such as acetoacetate and
beta-hydroxybutyrate. This occurs when the body is unable to use glucose for energy due
to a lack of insulin, causing it to break down fat stores instead, resulting in an
accumulation of ketones.

3. The normal pH of the plasma is approximately 7.35 to 7.45. In diabetic ketoacidosis, the
altered pH (7.20 in this case) results from the accumulation of ketones and the increased
production of hydrogen ions (H+) during the breakdown of fatty acids. This leads to an acidic
environment in the blood, also known as acidosis.

4. The Benedict's test is positive in this condition due to the presence of glucose in the
urine. In DKA, because of the lack of insulin, glucose cannot enter the cells and remains
 in the bloodstream, causing it to spill over into the urine. The Benedict's test detects the
presence of reducing sugars such as glucose in the urine.

5. The principle of the GOD-POD method involves the use of glucose oxidase to catalyze
the oxidation of glucose to gluconic acid and hydrogen peroxide (H2O2), which is then
detected using a peroxidase enzyme and a chromogen to produce a colored product. Other
enzymatic methods for measuring glucose include the hexokinase method and the glucose
dehydrogenase method, while non-enzymatic methods include the Folin-Wu method and
the Trinder reaction.

Case History: 2

A 43 year old diabetic male visits a diabetic clinic for a check-up. His previous visit to the
clinic was one month ago. He tells the doctor that he complies with all the dietary advice and
never misses insulin. His random plasma glucose level is 130 mg/dl, and blood HbA1c
concentration is 8% . Urine analysis did not show presence of glucose and ketone bodies.
Urine Microalbumin level is 250 mg/L.

1. What is HbA1c and how is it formed ? What is the reference range of HbA1c ?
2. What is the status of glycemic control in this person ?
3. What is the reference range of Microalbumin ? Comment on the urine
Microalbumin level of this person and mention its clinical significance.

1. HbA1c is a measure of average blood glucose levels over the past 2-3 months.
The reference range is less than 5.7%. HbA1c of 8% suggests poor glycemic
control.

2. The urine microalbumin level of 250 mg/L indicates microalbuminuria, an early

sign of kidney damage often linked to diabetes. It is clinically significant as it
signals potential kidney complications if not managed properly.

3. A urine microalbumin level of 250 mg/L in this person indicates

microalbuminuria, an early sign of kidney damage often associated with
diabetes. It is clinically significant as it signals potential kidney complications
if not managed properly.
Case history: 3

A 13 year old girl was admitted to hospital. Her mother mentioned that her daughter had been
losing weight and had polyuria. Doctor noticed a fruity breath. On admission the following
biochemical parameters of urine and blood were obtained.

Urine pH: 5.5

Urine glucose: 4+
Urine ketones: Moderate
Random plasma glucose : 480mg/dL
Anti GAD antibodies : positive
Serum Insulin : Decreased
Serum C Peptide : Decreased

1. What is the probable diagnosis? Justify.

2. What is the biochemical basis of fruity breath?
3. What is the biochemical basis of weight loss?
4. What is the advantage of serum C Peptide test over serum insulin test?

1. The probable diagnosis is Type 1 diabetes mellitus, supported by symptoms,

laboratory findings, and positive anti-GAD antibodies indicating severe insulin
deficiency.

2. The fruity breath in diabetes is due to the presence of ketones produced as a

result of fat breakdown for energy when insulin levels are low.

3. Weight loss in diabetes is caused by increased breakdown of fats and proteins

due to the body’s inability to use glucose effectively for energy.
 4.Serum C peptide test is advantageous over serum insulin test as it provides a more
stable and accurate measure of endogenous insulin production, especially in individuals
receiving exogenous insulin.

Case history: 4

A 22 year old patient with diabetic comes to the emergency department. She gives a 3 days
history of vomiting and abdominal pain. She is drowsy and her breathing is deep and rapid.
There is fruity smell from her breath.

1. What is the most likely diagnosis?

2. Which bedside tests could you do to confirm this diagnosis?
3. Which laboratory tests would you request further to corroborate your clinical findings?

1. The most likely diagnosis is diabetic ketoacidosis (DKA).

2. Bedside tests to confirm the diagnosis could include measuring blood glucose,
urine ketones, and blood ketones.

3.Further laboratory tests such as arterial blood gas analysis, serum electrolytes, serum
ketones, and complete blood count may be requested to corroborate the clinical findings.
Case history: 5:

A 45 year old obese male had a tooth infection, prior to extraction, he was advised to have a
routine blood and urine examination. The results were: Total WBC count-35,000/-cmm;
Differential count-P70, L20, E7, M2, B1; ESR-45mm/hr; Urine albumin-Trace; Urine sugar-
Orange precipitate; Urine ketone bodies- Nil, Urine bile salts- Nil, Urine bile pigments-Nil.

a) What are the further investigations to be done in this patient? Explain the rationale
behind each test.

b) When the diagnosis is confirmed and treatment started, how will you monitor the
patient?

c) What are the possible complications that can be avoided by proper monitoring of the
patient?

a) Further investigations may include blood culture, renal function tests, liver function
tests, fasting blood sugar, HbA1c, and dental imaging.

b) Monitoring would entail regular complete blood counts, renal and liver function tests,
blood sugar levels, and dental follow-ups.

c) Proper monitoring can help avoid complications such as sepsis, renal impairment,
diabetic complications, and liver complications.

GTT Chart 1

Below are the investigations findings in a person who underwent GTT. Patient’s HbA1c was
7.2%

Timing Plasma glucose level in mg/dL

Fasting 142

1 hr 289

2 hr 234
 3 hr 184

Questions:
1. Interpret the above GTT chart (1 mark)
2. Mention the criteria for diagnosis of the same (2 marks)
3. Mention the amount of glucose administered for GTT (1 mark)
4. Enumerate any two precautions to be taken before undergoing GTT (1 mark)
 GTT Chart 2

Below are the investigations findings in a person who underwent GTT. Patient’s HbA1c was
6.2%

Timing Plasma glucose level in mg/dL

Fasting 114

1 hr 197

2 hr 148

3 hr 111

Questions:
1. Interpret the above GTT chart (1 mark)
2. Mention the criteria for diagnosis of the same (2 marks)
3. Mention the amount of glucose administered for GTT (1 mark)
4. Enumerate any two precautions to be taken before undergoing GTT (1 mark)
 GTT Chart 3

Below are the investigations findings in a person who underwent GTT. Patient’s HbA1c was
5.7%

Timing Plasma glucose level in mg/dL

Fasting 117

1 hr 156

2 hr 136

3 hr 103

Questions:
1. Interpret the above GTT chart (1 mark)
2. Mention the criteria for diagnosis of the same (2 marks)
3. Mention the amount of glucose administered for GTT (1 mark)
4. Enumerate any two precautions to be taken before undergoing GTT (1 mark)

IEM

Case 1
A 4-year-old boy presented with Fatigue Paleness, Dark urine, Rapid heart rate, Shortness of
breath, Abdominal pain, Heart murmur, Enlarged spleen and liver, yellow skin and eyes. Past
history revealed recent administration of drug primaquine for the treatment for malaria.
His investigation revealed prolonged duration (>2weeks) of having jaundice. Family history
of similar episodes were seen in siblings.

The investigation revealed

Hb 8.5 g/dl RBC 3.5 x 108 /micro l

Hct 22% WBC 15 x 103 /micro l
ESR 1 Platelet 3.5 lakh/micro l
HbA1 96% Retic 3%
HbA2 3-5% MCV 50 fl
HbF <1% MCH 18 pg
Peripheral smear Bite cells MCHC 29 g/l
Serum total 12 mg/dl Serum conjugated 1 mg/dl
bilirubin bilirubin
Serum haptoglobin Decreased Serum LDH 500 IU/L
Urine Albumin -ve Urine glucose -ve
Urine ketone -ve Urine bile salts -ve
bodies
Urine bile pigments -ve Urine urobilinogen ++
Urine blood -ve

1. What is your probable diagnosis?

2. Justify the diagnosis?
3. What is the basis for family history of the disease?
4. What is the biochemical basis of pallor, dark urine?
5. What are the precipitating factors for the above manifestations?
6. What is the biochemical basis for precipitation of hemolysis and jaundice after
primaquine ingestion?
 Case 2

A 7-week-old baby girl is brought to the GP clinic and presents with vomiting, diarrhea, poor
feeding, and failure to thrive. The mother has recently noticed that the baby vomits or has
diarrhea after nursing. Findings on examination include cataract, jaundice, dry skin, pallor,
hepatomegaly, and poor tone.

Investigation revealed–

Blood analysis:

Plasma glucose- 50mg/dL

Elevation in serum galactose and RBC galactose-1-phosphate (Gal-1-P)

Serum total bilirubin- 8mg/dL, serum direct bilirubin- 1mg/dL.

GALT- deficient

Urine analysis:

Galactosuria, albuminuria, aminoaciduria.

Urine thin layer chromatography – galactose +

Urine GC/MS-High galactose, galactitol

1. What is the probable diagnosis?

2. Justify the diagnosis.
3. What is the biochemical cause for cataract?
4. What is the biochemical cause for pallor, hepatomegaly, hyperbilirubinemia and
jaundice?
5. What is the biochemical cause for albuminuria?
6. What is the biochemical cause for hypoglycemia?
7. What is the treatment for classical galactosemia?

1. The probable diagnosis is classical galactosemia.

2. The diagnosis is supported by the clinical presentation, elevated galactose-1-

phosphate levels, genetic analysis indicating GALT deficiency, and presence of galactose
in urine analysis.

3. Cataracts in galactosemia are caused by the accumulation of galactitol in the lens of

the eye.
 4. Hepatomegaly, hyperbilirubinemia, jaundice, and pallor result from impaired liver
function and bilirubin metabolism due to galactose accumulation.

5. Albuminuria in galactosemia is due to kidney damage from galactose metabolites.

6. Hypoglycemia in galactosemia results from the inability to convert galactose to

glucose.

7. The treatment for classical galactosemia involves dietary management, including

removing galactose and lactose from the infant's diet, and potential additional
treatments for complications such as cataracts and liver issues.

Case 3

3-year-old boy brought to emergency department after several episodes of vomiting and
lethargy. Boy had symptoms of failure to thrive. Such symptoms were first seen during
weaning when fruits were introduced into diet. Careful history evaluation found that these
episodes of vomiting and diarrhea because of certain type of food, especially high in
fructose. The glucometer recording showed 40mg/dL. He had lactic acidosis and serum
phosphate level of 1.4 mg/dl.

Urine analysis positive for Benedict’s test.

Enzymatic method specific for glucose is negative.

Paper Chromatogram showed positive for fructose.

 1. What is the probable diagnosis?
2. Justify the diagnosis.
3. What is the biochemical basis for the clinical symptoms?
4. What is the biochemical cause for hypoglycemia and low phosphate?
5. What is the treatment of the disorder?

Case 4

38 years old man came to the GP for routine investigation for purposes of life insurance. The
patient is in good health. He has no polydipsia, polyuria, pruritus, boils or other skin lesions,
no headaches, nor any minor complaints. At the age of 6, urine report showed positive for
sugar, on which on further investigation was identified as a pentose. No family history of
diabetes mellitus.

Laboratory Investigation:

Urine analysis positive for Benedict’s test.

Enzymatic method specific for glucose is negative.

Paper Chromatogram showed positive for pentose.

Case 5

An 3 month old infant was cranky and irritable, became quite lethargic between feedings,
and began to develop a potbelly. The baby also had two episodes of seizures. A physical
exam demonstrated an enlarged liver, while blood work taken between feedings
demonstrated elevated lactate, lipids and uric acid levels, as well as hypoglycemia.

1. What is the probable inborn error of metabolism the child is suffering from?
2. What is the enzyme that is defective in this case?
3. What is the biochemical basis of hyperuricemia?
4. What other tests can be done for confirmation of the disorder?
 Case 6
A two-year-old child was brought to the doctor with abdominal pain, bloating, flatulence,
nausea, and passing of bulky, frothy, and watery stools within a few hours after ingestion of
milk and dairy products. Hydrogen breath test performed with 2 g/kg lactose suspended in
water was 28ppm (cut-off 20 ppm).
1. What is the probable disorder the child is suffering from?
2. What is the enzyme that is defective in this case?
3. What other tests can be done for confirmation of the disorder?
4. Mention the basis of treatment in this case.